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At least 343 records · Page 19Linked to original sources
PubMed1986

Human MHC class III genes, Bf and C4. Polymorphism, complotypes and association with MHC class I genes in the Finnish population.

Electrophoretically detected genetic polymorphism of human MHC class III genes, factor B (Bf) and complement C4A and C4B, was studied in the Finnish population. Bf alleles were determined in a panel of sera from 70 unrelated individuals. The common Bf alleles, Bf*S and Bf*F, had frequencies of 73% and 26%, respectively. Only in 1 individual was another allele, Bf*F1, detected. The frequencies of the C4A and C4B alleles were based on studies of 254 unrelated individuals. In this panel, five different alleles were detected at the C4A locus and four at the C4B locus. At both loci an allele without a gene product, i.e. a 'null' allele, was observed with high frequency, 11% for C4A 'null' and 17% for C4B 'null'. The association of complotypes to HLA haplotypes was analyzed in 70 chromosomes. The most common combination, defined by class I and class III alleles, was HLA-B7-S31 (13%), followed by HLA-B35-F20 (8.4%) and HLA-B8-S03 (7.1%). Some HLA-B specificities, for example B15, B27 and B40, were associated with a variety of complotypes. The importance of complotyping in HLA genetics is discussed.

Complement C4↗
PubMed2004

Self-reactive memory-phenotype CD8 T cells exhibit both MHC-restricted and non-MHC-restricted cytotoxicity: a role for the T-cell receptor and natural killer cell receptors.

We have recently shown that interleukin-2 (IL-2)-activated CD8(+)CD44(hi) cells from normal mice express both adaptive and innate immune system receptors and specifically kill syngeneic tumor cells, particularly those that express NKG2D ligands. Here we show that CD8+ T cells from antigen-expressing H-Y T-cell receptor (TCR) transgenic mice also exhibit characteristics of both T cells and natural killer (NK) cells. Interaction with cognate self-antigen was required for the optimal expansion of these cells in peripheral lymphoid tissues. Although these cells possess a higher activation threshold relative to naive T cells, they can be activated by cytokine alone in vitro. They also undergo bystander proliferation in response to a bacterial infection in vivo. Interestingly, upon activation, the cells express the NKG2D receptor as well as the DNAX activation protein 12 (DAP12) adaptor protein. We provide evidence that NKG2D can act additively with the TCR in the killing of target cells, and it can also function as a directly activating receptor in non-major histocompatibility complex (MHC)-restricted killing of target cells. These properties of CD8+ T cells from H-Y TCR transgenic mice are remarkably similar to CD8(+)CD44(hi) cells that are found in normal mice. The H-Y TCR transgenic mice provide a well-defined system for characterizing the developmental biology and function of these cells.

Animals↗
PubMed2005

MHC class II expression through a hitherto unknown pathway supports T helper cell-dependent immune responses: implications for MHC class II deficiency.

MHC class II (MHCII) deficiency or bare lymphocyte syndrome (BLS) is a severe immunodeficiency characterized by deficient T helper (Th)-cell-dependent immunity. The disease is caused by defects of the MHCII promoter complex resulting in low or absent MHCII expression. We demonstrate in a murine model of MHCII deficiency (RFX5- or CIITA-deficient mice) that residual MHCII expression by professional antigen-presenting cells (APCs) is sufficient to support activation of adoptively transferred Th cells. Furthermore, upon transplantation of WT thymic epithelium, we observed development of endogenous Th cells with restoration of Th-cell-dependent antibody responses and immunity to cytomegalovirus infection, thus opening the possibility of an alternative treatment regimen for BLS. Residual MHCII expression was further induced by the presence of Th cells and also other stimuli. Analysis of CIITA/RFX5 double-deficient animals revealed that this inducible MHCII expression is genetically independent of the known promoter complex and thus constitutes an alternative MHCII expression pathway. In these experiments, we also detected a novel repressive function of the RFX complex in the absence of CIITA.

Animals↗
PubMed1991

Major histocompatibility complex (MHC) complement deficiency, ancestral haplotypes and systemic lupus erythematosus (SLE): C4 deficiency explains some but not all of the influence of the MHC.

In 1982 we reported that among Caucasians with systemic lupus erythematosus (SLE) there is an increased frequency of C4A null. As this allele occurs on the HLA-A1,B8,BfS, C4AQO,B1,DR3 (8.1) supratype, we suggested this accounted for the reported association of B8 and DR3. Since then we have shown that many supratypes including 8.1 identify unique segments of DNA conserved from a common but remote ancestor. Many of these ancestral haplotypes (AH), including 8.1, carry disease genes and some bear C4 null. We have therefore tested the hypothesis that in SLE C4 null alleles are directly involved by examining (1) whether all or only some AH bearing C4 null alleles are increased, (2) whether C4 null is increased in all racial groups examined, and (3) whether C4 null is associated with the presence of antinuclear antibodies (ANA) in the absence of SLE. We performed HLA and complement allotyping on 62 Australian Caucasians and 9 Australian aborigines with SLE and on the 10 out of 133 healthy individuals with 7 or more international units of ANA. Our data confirm an association of C4A null in Australian Caucasians (gene frequency 0.30 versus 0.15 in controls) and show an increased frequency of C4B null in Australian aborigines (gene frequency 0.33 versus 0.22). A review of an extensive literature shows C4A and/or C4B null are increased in all racial groups examined. On the other hand, the HLA-A3,B7,BfS,C4A3,B1,DR2 (7.1) AH rather than C4 null is associated with ANA in health. Our data indicate that while C4 nulls contribute to MHC susceptibility, other genes are likely to be involved.

Alleles↗
PubMed1989

Rheumatoid T lymphocyte MHC class II expression: in vitro stimulation produces normal MHC class II expression, independent of proliferation.

MHC Class II mediated immune responses, such as tuberculin PPD, are often subnormal in rheumatoid arthritis (RA). We investigated peripheral blood T lymphocyte proliferation and Class II expression after stimulation with phytohemagglutinin, OKT3 and tuberculin PPD, using double label immunofluorescence and flow cytometry. No difference was found in the percentage of Class II positive T lymphocytes or intensity of fluorescence of Class II between matched controls and patients with RA. A disparity between Class II expression and proliferation was noted, particularly in the 50% of patients with RA with poor proliferation to PPD, who showed normal Class II expression, indicating that these 2 functions are under separate control.

Adult↗
PubMed1985

Gamma-interferon enhances expression of Class I MHC antigens in the weakly HLA+ human choriocarcinoma cell line BeWo, but does not induce MHC expression in the HLA- choriocarcinoma cell line Jar.

PHA-activated lymphocyte supernatants and high doses of affinity-purified human gamma-interferon enhance the expression of apparently normal Class I histocompatibility antigens in a malignant human trophoblast cell line that expresses low amounts of these antigens under normal culture conditions. Another human choriocarcinoma cell line, Jar, which is normally HLA-, did not respond to this treatment. This system provides a model in which to study further the regulation and effects of MHC antigen expression in cells of trophoblastic origin.

Antibodies, Monoclonal↗
PubMed1997

MHC affinity, peptide liberation, T cell repertoire, and immunodominance all contribute to the paucity of MHC class I-restricted peptides recognized by antiviral CTL.

MHC class I-restricted T cell responses to viral proteins focus on a limited set of peptides. To better understand this phenomenon, we examined all of the 26 nonameric peptides encoded by the influenza virus A/Puerto Rico/8/34 (PR8) conforming to the canonical Kd binding motif. Ten peptides bound strongly to Kd as assessed by a cell surface stabilization assay. Five of these 10 induced in vitro secondary CD8+ T cell responses from splenocytes derived from PR8-immunized mice. The strongest responses were induced by the two previously defined antigenic peptides, which ranked only second and fifth in relative binding affinity. To examine the limiting factors in the immunogenicity of Kd-binding peptides, we produced recombinant vaccinia viruses (rVVs) expressing cytosolic or endoplasmic reticulum (ER)-targeted peptides. rVVs expressing ER-targeted versions of the 7 peptides with the highest relative affinities for Kd rescued Kd cell surface expression in T2 cells, while those expressing the 3 lowest affinity peptides did not. The immunogenicity of several, but not all, of the highest affinity peptides was greatly enhanced when expressed as VV-encoded cytosolic or ER-targeted peptides as compared with full length proteins. We conclude that limitations in the immunogenicity of class I binding peptides reflects, in order of decreasing importance, peptide liberation by cellular proteases, T cell repertoire, and TAP-mediated peptide transport. We also observed an additional important contributing factor: suppression of T cell responses to nondominant peptides by an immunodominant peptide located in the same protein.

Animals↗
PubMed1999

Characterization of Mhc-DRB allelic diversity in white-tailed deer (Odocoileus virginianus) provides insight into Mhc-DRB allelic evolution within Cervidae.

Although white-tailed deer (Odocoileus virginianus) are one of North America's best studied mammals, no information is available concerning allelic diversity at any locus of the major histocompatibility complex in this taxon. Using the polymerase chain reaction, single-stranded conformation polymorphism analysis, and DNA sequencing techniques, 15 DRB exon 2 alleles were identified among 150 white-tailed deer from a single population in southeastern Oklahoma. These alleles represent a single locus and exhibit a high degree of nucleotide and amino acid polymorphism, with most amino acid variation occurring at positions forming the peptide binding sites. Furthermore, twenty-seven amino acid residues unique to white-tailed deer DRB alleles were detected, with 19 of these occurring at residues forming contact points of the peptide binding region. Significantly higher rates of nonsynonymous than synonymous substitutions were detected among these DRB alleles. In contrast to other studies of Artiodactyla DRB sequences, interallelic recombination does not appear to be playing a significant role in the generation of allelic diversity at this locus in white-tailed deer. To examine evolution of white-tailed deer (Odvi-DRB) alleles within Cervidae, we performed a phylogenetic analysis of all published red deer (Ceel-DRB), roe deer (Caca-DRB), and moose (Alal-DRB) DRB alleles. The phylogenetic tree clearly shows a trans-species persistence of DRB lineages among these taxa. Moreover, this phylogenetic tree provides insight into evolution of DRB allelic lineages within Cervidae and may aid in assignment of red deer DRB alleles to specific loci.

Alleles↗
PubMed1992

Immunogenetics of collagen-induced arthritis in rats. Both MHC and non-MHC gene products determine the epitope specificity of immune response to bovine and chick type II collagens.

Seven inbred, RT1-congenic rat strains were immunized with native bovine (BII), porcine (PII), or chick (CII) type II collagen and observed for onset, incidence, and severity of arthritis. Clinical results were compared with IgG reactive with native rat type II collagen (RII) and the purified, renatured cyanogen-bromide peptides of BII, CII, or RII. Immunodominant responses to CB11, CB9,7, and CB12 of RII were identified. Secondary responses to CB8 and CB10 also occurred. Reproducible patterns of peptide reactivity were defined in each strain and reflected both RT1 and non-RT1 genotypes plus the species of immunizing collagen. BN non-RT1 gene products moderated clinical arthritis but increased the levels of reactivity to CB11 in three strains carrying RT1l,n,av1 haplotypes. WF (RT1u) rats were susceptible to collagen-induced arthritis (CIA) and developed very high levels of autoantibodies with dominant responses to rat CB11 after CII injections and to rat CB11 and CB9,7 after BII injections. DA (RT1av1) rats developed the most severe arthritis but had only moderate (total) levels of anti-RII IgG: a broad response to CB11, CB10, and CB9,7 after CII injections but predominantly to CB12 and CB9,7 after BII injections. Three RT1n strains--DA.1N(BN), WF.1N(MAXX), and BN--were resistant to BII-induced CIA but developed mild arthritis after immunization with CII. After BII: BN IgG reacted with CB9-7, CB11, and CB12; DA.1N and WF.1N IgG reacted with CB9,7 and CB12. After CII: BN IgG reacted broadly with CB11, CB9-7, CB12, and CB8; WF.1N IgG reacted to CB9-7, CB11, CB8, and CB12; DA.1N IgG reacted with CB8, CB11, and CB9-7. Thus, selective induction of CIA in BN, WF.1N, and DA.1N rats by CII correlated with serum IgG reactivity to rat CB11, but overall strain results identified no single cyanogen-bromide peptide as expressing the sole "arthritogenic" epitope in CIA.

Animals↗
PubMed1986

Molecular analysis of the rat MHC. I. Delineation of the major regions in the MHC and in the grc.

Southern blot analysis with liver DNA from a unique series of recombinant (R10, R11, R16, R18, R21, and R22), congenic (Y0.1U.grc+, Y0.1U.grc+/Y0.1L.grc, and Y0.1L.grc) and inbred rats has been performed to examine the restriction fragment length polymorphisms of class I genes. After digestion with Xba I or Eco RI, the genomic DNA was resolved on agarose gels, was transferred to nitrocellulose membranes, and was hybridized with murine H-2 cDNA probes. Eighteen to 25 bands of varying intensities could be clearly resolved in any given strain. Analysis of these hybridization patterns detected restriction fragment length polymorphisms that permitted the assignment of 17 specific fragments to regions within the major histocompatibility complex: RT1.A, RT1.B/D, and the RT1.E-grc-T1 alpha region. Fragments have been identified that are specific for grc, grc+, and RT1.E, and mark the junction sites between these loci. In addition, several markers identify the region around the sites of recombination in some strains. The hybridization pattern of the R18 recombinant had a unique band that specified a point of recombination within the grc. The recombinant R11 presented a unique restriction pattern unrelated to either of the parental strains or other related strains. This result suggests that R11 arose from a recombination event(s) undetected by conventional serologic methods.

Animals↗
PubMed1984

MHC- and non-MHC-encoded surface antigens of chicken lymphoid cells and erythrocytes recognized by polyclonal xeno-, allo- and monoclonal antibodies.

Surface antigens on chicken thymus and bursa cells were analyzed by immunoprecipitation using polyclonal and monoclonal antisera raised against (and specific for) thymus (ATS) or bursa (ABS) cells, respectively. The antigens identified were compared with those governed by the B-F, B-L and B-G regions of the chicken major histocompatibility complex (B complex). Four proteins were precipitated from thymus cells by 2 polyclonal ATS: both antisera recognized molecules of apparent molecular mass of 172-182, 132-135, 75-76 kDa, and one antiserum in addition recognized a protein of 102 kDa. The 172-182 and 102-kDa peaks were still demonstrable under reducing conditions indicating that they are composed of a single polypeptide chain, the other 2 were lost under reducing conditions, therefore, must be composed of smaller subunits. Of the 2 monoclonal ATS tested, one identified a single protein of 186 kDa and the other a 135-kDa protein (in addition to 2 smaller molecules); whether these are the same as those precipitated by the polyclonal antisera remains to be determined as they behaved differently under reducing conditions. Proteins of 162 and 78-84 kDa were revealed by 2 polyclonal ABS under nonreducing conditions but the former may in one case be a polymer (it disappeared under reducing conditions) and in the other a single molecule. In addition molecules of 182 kDa were identified by one antiserum and of 84 and 60 kDa by the other under nonreducing conditions. Of the 4 monoclonal ABS only one identified a 200-kDa protein: molecules of 115-125, 90-100, 48-52 and 40-43 kDa were also precipitated, all of which were reduced to smaller molecules. With 2 specific anti-B-F alloantisera we were able to precipitate the "conventional" B-F antigen from red blood cell lysates of CB-strain chickens resolving into a 40-kDa peak and a light chain of about 12 kDa corresponding to beta 2 microglobulin. Precipitates from peripheral blood lymphocytes, bursa and thymus cells revealed an additional protein of 22 kDa. With 2 specific B-L alloantisera two peaks of 33 kDa and 31 kDa were obtained from peripheral blood lymphocytes. Using anti-B-G alloantisera a double band corresponding to 47 and 42 kDa was seen under reducing conditions. There is no evidence from these data to indicate that the polyclonal and monoclonal antibodies are directed towards major histocompatibility complex antigens.

Animals↗
PubMed1988

Epitopes associated with major histocompatibility complex (MHC) restriction site of T cells. IV. I-J epitopes on MHC-restricted cloned T cells.

We studied the expression of an I-Jk epitope on class II-restricted cloned L3T4+ T cells established from H-2k, H-2b, F1 and semiallogeneic radiation bone marrow chimeras by the inhibition of antigen-induced T cell proliferation and in vitro secondary antibody response, and by the direct immunofluorescence with a monoclonal anti-I-Jk. Both I-Ak- and I-Ek-restricted T cells were shown to carry the identical I-Jk epitope regardless of their genotypic origins, antigen specificity, and helper or suppressor function. None of the I-Ab-restricted clones derived from similar animals showed the I-Jk epitope. This isomorphism, regardless of the restriction specificity for I-Ak or I-Ek, contradicts the idea that I-J is an idiotypic determinant on class II-restricted T cell antigen receptor (TcR). In fact, the I-Jk epitope was not comodulated with TcR/T3 complex when incubated with an anti-T3 antibody, indicating that I-J is a new isomorphic receptor for self different from TcR alpha/beta heterodimers.

Animals↗
PubMed1982

Cell-mediated cytotoxicity to non-MHC alloantigens on mouse epidermal cells. VI. Influence of the MHC on the tissue specificity of cytotoxic T-lymphocyte responses.

Mice of the C3H/He and A non-H-2 backgrounds are disparate from mice of the B10 background for the tissue-restricted, non-H-2 alloantigen of epidermal cells (EC), Epa-1, that is expressed by EC but not by lymphocytes (LC), as well as for a number of other alloantigens of the B10 background that are expressed by both EC and LC, generically referred to as "lymphocyte/epidermal alloantigens" (LEA). In this study, we compared the ability of various H-2 congenic strains on the C3H or A backgrounds to mount cytotoxic T-lymphocyte (CTL) responses to EC from H-2 compatible mice of the B10 background. High responses to Epa-1 were detected only in the H-2a and H-2k haplotypes; H-2b, H-2o1, H-2s, H-2t1, and H-2t2 haplotypes were nonresponders to Epa-1. High responses to LEA were detected in H-2a, H-2b, H-2s, H-2t1, and H-2t2 haplotypes; H-2k and H-2o1 were nonresponsive to LEA. Analysis of the H-2K, I and D region alleles of responders indicates that H-2Kk is essential for anti-Epa CTL responses, whereas Dd, Db or Ks were all permissive for strong anti-LEA responses. The ability to mount a given CTL response was not associated with differences in I-region alleles. These results are discussed in terms of K/D region products serving as Ir-gene products for CTL and in determining the apparent tissue-specificity of CTL.

Animals↗