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PubMed2003

The E5 protein of human papillomavirus type 16 perturbs MHC class II antigen maturation in human foreskin keratinocytes treated with interferon-gamma.

Major histocompatibility complex (MHC) class II antigens are expressed on human foreskin keratinocytes (HFKs) following exposure to interferon gamma. The expression of MHC class II proteins on the cell surface may allow keratinocytes to function as antigen-presenting cells and induce a subsequent immune response to virus infection. Invariant chain (Ii) is a chaperone protein which plays an important role in the maturation of MHC class II molecules. The sequential degradation of Ii within acidic endocytic compartments is a key process required for the successful loading of antigenic peptide onto MHC class II molecules. Since human papillomavirus (HPV) 16 E5 can inhibit the acidification of late endosomes in HFKs, the E5 protein may be able to affect proper peptide loading onto the MHC class II molecule. To test this hypothesis, HFKs were infected with either control virus or a recombinant virus expressing HPV16 E5 and the infected cells were subsequently treated with interferon-gamma. ELISAs revealed a decrease of MHC class II expression on the surface of E5-expressing cells compared with control virus-infected cells after interferon treatment. Western blot analysis showed that, in cells treated with interferon gamma, E5 could prevent the breakdown of Ii and block the formation of peptide-loaded, SDS-stable mature MHC class II dimers, correlating with diminished surface MHC class II expression. These data suggest that HPV16 E5 may be able to decrease immune recognition of infected keratinocytes via disruption of MHC class II protein function.

Antigens, Differentiation, B-Lymphocyte↗
PubMed2000

Distribution of MHC-II and CD1 molecules in the skin of lambs and changes during experimentally-induced contact hypersensitivity.

The presentation of antigen to specific T-cell populations is a crucial event during the elicitation phase of contact hypersensitivity (CHS). Significant changes in CD4(+) T-cell and gammadelta T-cell populations occur in the skin of sheep 48h after re-exposure to dinitrochlorobenzene but the expression of antigen presentation molecules such as MHC-II and CD1 at this stage of the hypersensitivity response has not been investigated. In the present study, a panel of monoclonal antibodies recognising CD1 and MHC-II subtypes was used in combination with computer assisted morphometric analysis to estimate the distribution of antigen presentation molecules in the superficial and deep dermis of the ears of lambs during the elicitation phase of CHS. The MHC-II molecules showed predominantly a perivascular and peri-appendageal distribution in the dermis and there were scattered MHC-II(+) cells in the basal and suprabasal layers of the epidermis. The CD1w2(+) (CD1b-like) molecules were present on distinct cells that were scattered evenly through the dermis, whereas CD1w3(+) (CD1c-like) molecules were almost exclusively detected on or in close association with the vascular endothelium. There was a significant increase in the presence of MHC-DQ(+) cells in the superficial dermis of dinitrochlorobenzene-treated animals compared with both an untreated control group and a vehicle-treated control group. However, MHC-DQ/DR(+) and CD1w3(+) cells only showed a significant increase compared with the vehicle-treated control group. The present study shows that the distribution of molecules involved in antigen presentation to CD4(+) T-cells and gammadelta T-cells changes during the elicitation phase of CHS in sheep, and suggests a role for MHC-DQ molecules on antigen presenting cells. However, the changes in distribution and expression of MHC-II and CD1 subtypes argue against a prominent role for a CD1-dependent pathway for T-cell recognition in the clinical cutaneous hypersensitivity response in sheep. Based on the expression of MHC-II molecules and CD1c molecules, we also suggest a potential role for endothelial cells in antigen presentation during the clinical dermatitis reaction.

Animals↗
PubMed1991

Resistance to NK cell-mediated cytotoxicity (in K-562 cells) does not correlate with class I MHC antigen levels.

Natural Killer (NK) cells probably function as an early line of defense against virus-infected cells and tumor cells. In all cases, the killing by NK cell-mediated cytotoxicity (NK-CMC) is not MHC-restricted and the factors which determine the sensitivity to NK-CMC have not yet been identified. A positive correlation between resistance to NK-CMC and the level of class I MHC antigen (MHC I) expression on target cells has been reported in many studies, and in some cases a functional linkage between the two has been claimed. Several other studies have shown that there is no such correlation. By employing several experimental systems, we demonstrate here a lack of correlation between the level of MHC I and the sensitivity of K-562 cells to NK-CMC. Transfer of MHC I to MHC I-negative cells via vesicles had no effect on their resistance to NK-CMC. In addition, a decrease in resistance to NK-CMC and increase of MHC I levels was observed following target-cell membrane modulation by both application of cholesterol and hydrostatic pressure. Finally, no correlation between sensitivity to NK-CMC and MHC I expression was found in three sublines of K-562 cells. Since NK-CMC is a multistage process, it is concluded that components other than class I MHC antigens have a more prominent role in modulating the sensitivity of target cells to NK-CMC.

Cell Death↗
PubMed2000

Loss of MHC class II expression is associated with a decrease of tumor-infiltrating T cells and an increase of metastatic potential of colorectal cancer: immunohistological and histopathological analyses as compared with normal colonic mucosa and adenomas.

We immunohistologically investigated 76 cases of primary colorectal cancer and 13 cases of adenoma to clarify the relationship of MHC class II expression with the grade of differentiation, the density of tumor-infiltrating lymphocytes, and the incidence of metastasis to lymph nodes. MHC class II expression was mostly negative in normal colonic epithelium. In contrast, 32 out of 76 cases (42%) of cancer and five out of 13 cases (38%) of adenoma were positive for MHC class II. MHC class II expression was higher in well-differentiated than in poorly differentiated adenocarcinoma. The density of infiltrating lymphocytes was higher in cancer than in the normal mucosa, and higher in MHC class II-positive tissues than in negative lesions. The incidences of lymphatic invasion and cancer metastasis to lymph nodes were definitely higher in MHC class II-negative cancers than in MHC class II-positive cancers. MHC class II was rarely expressed in metastatic cancer cells of lymph nodes. These results indicated that the loss of MHC class II is correlated with the incidence of metastasis to regional lymph nodes.

Adenocarcinoma↗
PubMed1998

The thiol oxidoreductase ERp57 is a component of the MHC class I peptide-loading complex.

The proper folding and assembly of major histocompatibility complex (MHC) class I molecules in the endoplasmic reticulum (ER) is an intricate process involving a number of components. Nascent heavy chains of MHC class I molecules, translocated into the ER membrane, are rapidly glycosylated and bind the transmembrane chaperone calnexin. In humans, after dissociation from calnexin, fully oxidized MHC class I heavy chains associate with beta 2-microglobulin (beta 2m) and the soluble chaperone calreticulin. This complex interacts with another transmembrane protein, tapasin, which is believed to assist in MHC class I folding as well as in mediating the interaction between assembling MHC class I molecules and the transporter associated with antigen processing (TAP). The TAP heterodimer (TAP1-TAP2) introduces the final component of the MHC class I molecule by translocating peptides, predominately generated by the proteasome, from the cytosol into the ER where they can bind dimers of beta 2M and the MHC class I heavy chain. Recently, the thiol oxidoreductase ERp57--also known as GRP58, ERp61, ER60, Q2, HIP-70, and CPT and first misidentified as phospholipase C-alpha--has been shown to bind in conjunction with calnexin or calreticulin to a number of newly synthesized ER glycoproteins when their N-linked glycans are trimmed by glucosidases I and II. It was speculated that ERp57 is a generic component of the glycan-dependent ER quality control system. Here, we show that ERp57 is a component of the MHC class I peptide-loading complex. ERp57 might influence the folding of MHC class I molecules at a critical step in peptide loading.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

MHC-dependent survival of naïve T cells? A complicated answer to a simple question.

The differentiation and survival of developing alpha beta thymocytes depends on effective T-cell receptor (TCR) signaling upon recognition of self peptide/major histocompatibility complex (MHC) molecule ligands. Although this concept is uniformly accepted with regard to immature thymocytes, there are conflicting reports as to whether or not MHC recognition is required for survival of mature peripheral naïve T cells. In this review, we assess these reports critically and conclude that in many cases, the differences observed in CD4(+) T-cell recovery between MHC-expressing and MHC-deficient animals can be attributed to proliferation occurring only in the MHC-expressing lymphopenic animals studied in these models systems, rather than to effects of MHC recognition on cell viability per se. Still other reports involve experimental manipulations that may have affected the intrathymic development of the T cells such that they receive a "poor" selecting signal, fail to fully mature, and thus behave more like thymocytes in their survival characteristics (i.e., show MHC dependence). With respect to CD8(+) T cells, we discuss data suggesting that some clones are more dependent upon the presence of MHC class I for survival than others. We propose that some CD8(+) T cells even in a wild-type host may behave like the manipulated CD4(+) T cells just described, and fail to mature completely with respect to their survival requirements. Although the proportion of CD8(+) cells in this MHC-dependent state is not known, the corresponding fraction among CD4(+) T cells seems to be rather small. Overall, our analysis of the available data suggests that most or all mature CD4(+) (and perhaps also many CD8(+)) T lymphocytes do not depend on self-recognition for their viability in the periphery.

Animals↗
PubMed2003

Genetic variation of microsatellite loci in the major histocompatibility complex (MHC) region in the southeast Asian house mouse (Mus musculus castaneus).

Major histocompatibility complex (MHC) genes are the most polymorphic loci known for vertebrates. Here we employed five microsatellite loci closely linked to the MHC region in an attempt to study the amount of genetic variation in 19 populations of the southeast Asian house mouse (Mus musculus castaneus) in Taiwan. The overall polymorphism at the five loci was high (He = 0.713), and the level of polymorphism varied from locus to locus. Furthermore, in order to investigate if selection is operating on MHC genes in natural mouse populations, we compared the extent and pattern of genetic variation for the MHC-linked microsatellite loci (the MHC loci) with those for the microsatellite loci located outside the MHC region (the non-MHC loci). The number of alleles and the logarithm of variance in repeat number were significantly higher for the MHC loci than for the non-MHC loci, presumably reflecting linkage to a locus under balancing selection. Although three statistical tests used do not provide support for selection, their lack of support may be due to low statistical power of the tests, to weakness of selection, or to a profound effect of genetic drift reducing the signature of balancing selection. Our results also suggested that the populations in the central and the southwestern regions of Taiwan might be one part of a metapopulation structure.

Animals↗
PubMedDate not supplied

Use of the MHC for mate choice in wild house mice (Mus domesticus).

The mechanisms maintaining natural diversity at the major histocompatibility complex (MHC) are not well understood. To increase knowledge of one potential mechanism, I examined the use of MHC genes for mate choice by wild house mice in a controlled laboratory setting. Three rearing groups of wild test mice were produced: non-fostered control mice, mice fostered into families of an inbred laboratory mouse strain, and mice fostered into families of a second, MHC-congenic mouse strain. Mature test mice were given a choice of two opposite-sex stimulus mice from the two MHC-congenic strains used for fostering, and were scored for several measures of preference. The results were non-significant in general, but females of two rearing groups spent significantly more time with mice of one MHC-type, and in most rearing groups, mice tended to spend more time with this same MHC-type. Other results showed that male test mice ejaculated indiscriminantly and that female wild mice mated to ejaculation more often in longer length trials, but showed no significant preferences. In this study, fostering seemed to have little or no effect on MHC-based mate preferences of wild house mice, and wild mice did not appear to be using the MHC to avoid inbreeding. However, some wild female mice used the MHC to choose potential mates.

Animals↗
PubMed1994

Production of soluble MHC class II proteins with covalently bound single peptides.

The alpha beta T-cell receptors (TCRs) react with complex ligands composed of peptides bound to major histocompatibility complex (MHC) proteins. In the absence of foreign antigens the peptides bound to MHC molecules come from the proteins of the host itself. Interactions between TCRs and these self-peptide-MHC ligands work positively to drive T-cell development in the thymus and negatively to delete or inactivate T cells with potential self-reactivity. On the cell surface, MHC proteins are associated with many different self peptides, making it impossible to know which self peptide was involved in positive or negative interactions with a particular T cell. These studies as well as in vitro studies on TCR-peptide-MHC interactions would be aided by a means of producing MHC molecules containing a single peptide. We have tackled this problem for MHC class II proteins by genetically attaching the peptide by a flexible peptide linker to the amino terminus of the class II beta-chain. Here we report that a secreted, soluble form of this covalent peptide-MHC complex can be expressed in insect cells. The peptide is engaged by the peptide-binding groove of the secreted MHC molecule and this complex is recognized by T cells bearing receptors specific for that combination.

Amino Acid Sequence↗
PubMed2006

Surface expression of MHC class II in dendritic cells is controlled by regulated ubiquitination.

Dendritic cells have a unique function in the immune response owing to their ability to stimulate immunologically naive T lymphocytes. In response to microbial and inflammatory stimuli, dendritic cells enhance their capacity for antigen presentation by a process of terminal differentiation, termed maturation. The conversion of immature to mature dendritic cells is accompanied by a marked cellular reorganization, including the redistribution of major histocompatibility complex class II molecules (MHC II) from late endosomal and lysosomal compartments to the plasma membrane and the downregulation of some forms of endocytosis, which has been thought to slow the clearance of MHC II from the surface. The relative extent to which these or other mechanisms contribute to the regulation of surface MHC II remains unclear, however. Here we find that the MHC II beta-chain cytoplasmic tail is ubiquitinated in mouse immature dendritic cells. Although only partly required for the sequestration of MHC II in multivesicular bodies, this modification is essential for endocytosis. Notably, ubiquitination of MHC II ceased upon maturation, resulting in the accumulation of MHC II at the cell surface. Dendritic cells thus exhibit a unique ability to regulate MHC II surface expression by selectively controlling MHC II ubiquitination.

Amino Acid Sequence↗
PubMed2003

Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2K(b).

The Ly49 family of natural killer (NK) receptors regulates NK cell function by sensing major histocompatibility complex (MHC) class I. Ly49 receptors show complex patterns of MHC class I cross-reactivity and, in certain cases, peptide selectivity. To investigate whether specificity differences result from topological differences in MHC class I engagement, we determined the structure of the peptide-selective receptor Ly49C in complex with H-2K(b). The Ly49C homodimer binds two MHC class I molecules in symmetrical way, a mode distinct from that of Ly49A, which binds MHC class I asymmetrically. Ly49C does not directly contact the MHC-bound peptide. In addition, MHC crosslinking by Ly49C was demonstrated in solution. We propose a dynamic model for Ly49-MHC class I interactions involving conformational changes in the receptor, whereby variations in Ly49 dimerization mediate different MHC-binding modes.

Animals↗
PubMed2001

Ubiquitination is essential for human cytomegalovirus US11-mediated dislocation of MHC class I molecules from the endoplasmic reticulum to the cytosol.

Human cytomegalovirus encodes two glycoproteins, US2 and US11, which cause rapid degradation of MHC class I molecules, thus preventing recognition of virus-infected cells by the immune system. This degradation process involves retrograde transport or 'dislocation' of MHC class I molecules from the endoplasmic reticulum (ER) to the cytosol, where they are deglycosylated by an N-glycanase and degraded by the proteasome. At present it is unknown whether ubiquitination is required for US2- and US11-mediated dislocation and degradation of MHC class I molecules. Here, we show that in E36ts20 hamster cells, which contain a temperature-sensitive mutation in the E1 ubiquitin-activating enzyme, US11-mediated degradation of MHC class I molecules is strongly impaired at the non-permissive temperature, indicating the necessity for ubiquitination in this process. We next addressed the question of whether ubiquitination is a condition for the retrograde movement of MHC class I molecules from the ER to the cytosol, or whether ubiquitination is merely required for recognition of dislocated MHC class I molecules by the proteasome. In the absence of a functional ubiquitin system, complexes of US11 and MHC class I molecules accumulate in the ER. In this state the membrane topology of MHC class I molecules does not significantly change, as judged from proteinase K digestions. Thus the results indicate that a functional ubiquitin system is essential for dislocation of MHC class I molecules from the ER to the cytosol.

Animals↗
PubMed2000

MHC class I pathway is not required for the development of crescentic glomerulonephritis in mice.

MHC II and CD4+ T cells are required for anti-glomerular basement membrane (GBM) globulin-initiated crescentic glomerulonephritis (GN) in mice, but the role of MHC I and CD8+ T cells is unclear. The cytolytic function of CD8+ T cells requires recognition of peptide antigens presented on MHC I. CD8+ T cells can also perform helper functions via cytokine production. The contribution of MHC I to crescentic GN was investigated using TAP-1 gene knock out (TAP-1-/-) mice, which have deficient MHC I antigen presentation. Heterozygous TAP-1 mice have normal MHC I expression and developed GN with crescents in 42 +/- 4% of glomeruli (normal 0%), proteinuria (9.1 +/- 1.6 mg/20 h, normal 1.5 +/- 0.3 mg/20 h) and impaired renal function (creatinine clearance 110 +/- 8 microl/min, normal 193 +/- 10 microl/min) following administration of sheep anti-mouse GBM globulin. TAP-1-/- mice, which have extremely low MHC I expression and reduced CD8+ T cells, developed similar GN with 39 +/- 3% crescents, proteinuria (12.7 +/- 4.3 mg/20 h) and impaired renal function (creatinine clearance 123 +/- 20 microl/min). In vivo antibody-induced CD8 depletion did not attenuate crescent formation or protect renal function in C57Bl/6 mice developing GN, although significant reduction in proteinuria (5.3 +/- 1.2 mg/20 h, P = 0. 012) and glomerular recruitment of CD4+ T cells and macrophages were observed compared with control treated mice with GN. These data demonstrate that MHC I is not required for development of crescentic GN in mice. The MHC I-independent contribution of CD8+ T cells to proteinuria and inflammatory cell recruitment suggests that they may serve a 'helper' rather than cytolytic role in this disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Differential expression of MHC class II molecules by microglia and neoplastic astroglia: relevance for the escape of astrocytoma cells from immune surveillance.

There is increasing evidence that microglia serve as antigen presenters in the human CNS. Although the occurrence of MHC class II immunoreactive cells has been reported in astrocytic gliomas, the relative contribution of microglia to this cell population has not been studied in detail. Using computer-assisted image analysis, we have investigated the expression of MHC class II molecules and of the microglia/macrophage markers Ki-MIP, RCA-1, KP1 and iba1, in 97 astrocytic gliomas comprising all WHO grades to answer the question whether there is a correlation between tumour grade and the number of MHC class II positive microglia/macrophage profiles. Microglia expressing MHC class II were common in astrocytomas and anaplastic astrocytomas but rare in pilocytic tumours although there was significant variation within each group. MHC class II immunoreactivity was reduced in highly cellular areas of glioblastomas where large numbers of cells expressing macrophage markers were still present. Thus, there was no simple relationship between tumour grade and microglial/macrophage MHC class II expression. In addition, up to 55% of astrocytic gliomas contained MHC class II immunoreactive tumour cells. Microglia but not tumour cells were found to express the BB1/B7 costimulator. We conclude that microglia in astrocytic gliomas are well equipped to function as antigen presenting cells. Yet, neoplastic astroglia appear to acquire the capacity to downregulate microglial MHC class II expression and, at the same time, may induce T-cell clonal anergy through aberrant expression of MHC class II molecules.

Antigen Presentation↗
PubMed1999

Transplant surgery injury recruits recipient MHC class II-positive leukocytes into the kidney.

BACKGROUND: CD4 T cells, which are stimulated by the "indirect pathway" of antigen-presentation, participate in rejection. These T cells are sensitized by recipient major histocompatibility complex (MHC) class II-positive leukocytes that migrate into the transplant. Therefore, an important early step in rejection is the immigration of these recipient MHC class II-positive leukocytes into the renal transplant. The regulation of this early step is not understood. We now test the hypothesis that such leukocytes immigrate into the renal transplant in response to ischemic injury occurring during the transplant procedure. METHODS: We transplanted Brown Norway (BN) kidneys into F1 Lewis/Brown Norway (L/BN) recipients. The F1 recipients are tolerant to the parental BN antigens, and any infiltration of recipient MHC class II-positive leukocytes results from injury occurring during transplantation surgery. In addition, ischemia/reperfusion injury was also induced by temporarily occluding the native renal arteries for 30 minutes. Transplanted kidneys and native kidneys, which suffered ischemia/reperfusion injury, were studied by immunohistochemistry on days 3, 7, 14, and 28 after surgery. Staining by the new monoclonal antibody (mAb) OX62 and antibodies to MHC class II identified dendritic cells. In addition, the following monoclonal antibodies identified: gamma/delta T cells, V65; B cells, OX33; cells that may be macrophages, dendritic cells, or dendritic cell precursors, ED1 (+) and OX62 (-); and recipient class II MHC, OX3. RESULTS: After transplantation, the serum creatinine increased to 4 mg/dl and then decreased, which was consistent with reversible injury during transplantation and the absence of rejection. We found that the injury of transplantation itself resulted in the infiltration of recipient MHC class II-positive leukocytes into the transplanted kidney. This infiltrate peaked at days 7 to 14 after surgery. The inflammation was peritubular and patchy and involved cortex and outer medulla. Double staining for OX62 and OX3 identified some of the infiltrating leukocytes as dendritic cells. Other recipient leukocytes were MHC class II positive, ED1 positive, and OX62 negative. We also found that MHC class II leukocytes, including dendritic cells, infiltrated native kidneys injured by ischemia/reperfusion injury. CONCLUSION: To our knowledge, this is the first demonstration that injury to the kidney during transplantation recruits recipient MHC class II-positive leukocytes into the kidney. Some of these leukocytes are dendritic cells.

Animals↗
PubMed2006

Functional CD8+ but not CD4+ T cell responses develop independent of thymic epithelial MHC.

The role of nonthymic epithelial (non-TE) MHC in T cell repertoire selection remains controversial. To analyze the relative roles of thymic epithelial (TE) and non-TE MHC in T cell repertoire selection, we have generated tetraparental aggregation chimeras (B6-nude<=>BALB/c and B6<=>BALB/c-nude) harboring T and B cells from both parents, whereas TE cells originated exclusively from the non-nude donor. These chimeras mounted protective virus-specific TE and non-TE MHC-restricted T cell responses. To further evaluate whether non-TE MHC alone was sufficient to generate a functional T cell repertoire, we generated tetraparental aggregation chimeras lacking MHC class II (B6-nude<=>MHCII(-/-)) or both MHC molecules (B6-nude<=>MHCI(-/-)II(-/-)) on TE cells, but not on cells of B6-nude origin. Chimeras with MHC-deficient TE cells mounted functional virus-specific CD8+ but not CD4+ T cell responses. Thus, maturation of functional CD4+ T cell responses required MHC class II on thymic epithelium, whereas CD8+ T cells matured in the absence of TE MHC.

Animals↗
PubMed2003

Variable hematopoietic graft rejection and graft-versus-host disease in MHC-matched strains of mice.

MHC typing for human hematopoietic cell transplantation (HCT) from unrelated donors is currently performed by using a combination of serologic and molecular techniques. It has been determined that allelic differences in human MHC molecules, revealed by nucleotide sequencing but not by serologic typing, substantially influence graft rejection and graft-versus-host disease, two serious complications of clinical HCT. We studied transplantation of purified hematopoietic stem cells in a series of mouse strains that were matched at the MHC but had different background genes, and we observed striking differences in engraftment resistance and graft-versus-host disease severity, both factors depending on the donor-recipient strain combination. The individual mouse lines studied here were established nearly a century ago, and their MHC types were determined exclusively by serologic techniques. We considered the possibility that serologically silent MHC polymorphisms could account for our observations and, therefore, we performed DNA sequencing of the class I and II MHC alleles of our mouse strains. At each locus, exact homology was found between serologically MHC-matched strains. Our results likely extend to all serologically MHC-matched mouse strains used in modern research and highlight the profound and variable influence that non-MHC genetic determinants can have in dictating outcome after HCT.

Alleles↗
PubMed1999

Trafficking of spontaneously endocytosed MHC proteins.

Class I MHC protein primarily presents endogenous antigen but also may present exogenous antigen. Here, we investigated the intracellular pathway of spontaneously internalized class I MHC protein by confocal microscopy. beta(2)-microglobulin (beta(2)m), labeled with a single fluorophore, was exchanged at the surface of B cell transfectants to specifically mark cell surface and endocytosed class I MHC protein. Intracellular beta(2)m colocalized with fluorophore-conjugated transferrin, implying that class I MHC protein endocytosed into early endosomes. These endosomes containing fluorescent beta(2)m were found close to or within the Golgi apparatus, marked by fluorescent ceramide. Even after 24 hr of incubation, very little fluorescent beta(2)m was found in intracellular organelles stained by DiOC(6), marking the endoplasmic reticulum, or fluorophore-conjugated low density lipoprotein, marking late endosomes and lysosomes. Fluorophore-conjugated superantigens (staphylococcal enterotoxin A and B), presumed to enter cells bound to class II MHC protein, also were found to endocytose into beta(2)m-containing early endosomes. Staining with mAb and use of transfectants expressing MHC protein attached to green fluorescent protein confirmed the presence of intracellular compartments rich in both class I and II MHC protein and demonstrated that class I and II MHC protein also colocalize in discrete microdomains at the cell surface. These cell surface microdomains also contained transferrin receptor and often were juxtaposed to cholesterol-rich lipid rafts. Thus, class I and II MHC protein meet in microdomains of the plasma membrane and endocytose into early endosomes, where both may acquire and present exogenous antigen.

B-Lymphocytes↗