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At least 721 records · Page 40Linked to original sources
PubMed2001

T-cell epitope analysis on the autoantigen phogrin (IA-2beta) in the nonobese diabetic mouse.

The protein tyrosine phosphatases (PTPs) IA-2 and phogrin (IA-2beta) are major autoantigens in type 1 diabetes that possess common serological epitopes in their COOH termini. The epitopes recognized by the T-cells that cause the disease, however, remain to be defined. Eight phogrin-specific T-cell clones were generated from NOD mice, and their epitopes were mapped. The mapping was performed initially with recombinant gluthathione S-transferase-phogrin COOH deletion constructs and ultimately with overlapping synthetic peptides. Two dominant epitopes were identified: one (aa 629-649) immediately adjacent to the transmembrane domain (aa 604-628) and the second (aa 755-777) lying in the NH(2)-terminal region of the conserved PTP domain. T-cells that are specific to either of these peptides and that could destroy islet tissue in vivo though spontaneous T-cell proliferative responses were observed in prediabetic female NOD splenocytes only to the aa 755-777 epitope. In NOD female mice immunized with the epitope peptide, intramolecular determinant spreading occurred from the aa 629-649 epitope to the aa 755-777 epitope but not in the opposite direction. We concluded that the initial T-cell response to phogrin is restricted to a small number of dominant peptides and that it subsequently spreads to other regions of the molecule, including those containing the major humoral epitopes that are highly conserved between IA-2 and phogrin.

Amino Acid Sequence↗
PubMed1991

The alpha-galactosyl epitope on human normal and autoimmune thyroid cells.

As much as 1% of circulating IgG in man (the natural anti-Gal antibody) is directed against the alpha-galactosyl epitope, with the structure Gal alpha 1----3Gal beta 1----4GlcNAc-R. The alpha-galactosyl epitope is abundantly expressed on cells of nonprimate mammals, prosimians, and New World monkeys. Its expression is diminished in Old World monkeys, apes, and humans. It has been previously suggested that interaction between anti-Gal and aberrantly expressed alpha-galactosyl epitopes on thyroid cells may contribute to the initiation of autoimmune thyroid disorders. To study this possibility, alpha-galactosyl epitope expression on thyroid cell membranes of normal individuals and patients with Graves' disease was assessed by a sensitive radioimmunoassay. alpha-Gal-actosyl epitopes were found both on normal and diseased thyroid cells. Whereas the concentration of these epitopes on Graves' disease thyroid membranes was somewhat higher than that observed in normal glands, the difference was not significant. The activity of the enzyme, alpha 1-3-galactosyltransferase, which synthesizes the alpha-galactosyl epitope, was higher in microsomal fractions obtained from some patients as compared with healthy controls, but not significantly different. In view of the abundance of anti-Gal antibody in the circulation, it is argued that, under physiologic conditions, the interaction of this antibody with alpha-galactosyl epitopes does not elicit pathologic effects. However, aberrant expression of the alpha-galactosyl epitope may result in effective anti-Gal binding to thyroid cells (e.g., rearrangement of this structure on the cell membrane or its increased expression).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Abrogation of CTL epitope processing by single amino acid substitution flanking the C-terminal proteasome cleavage site.

CTL directed against the Moloney murine leukemia virus (MuLV) epitope SSWDFITV recognize Moloney MuLV-induced tumor cells, but do not recognize cells transformed by the closely related Friend MuLV. The potential Friend MuLV epitope has strong sequence homology with Moloney MuLV and only differs in one amino acid within the CTL epitope and one amino acid just outside the epitope. We now show that failure to recognize Friend MuLV-transformed tumor cells is based on a defect in proteasome-mediated processing of the Friend epitope which is due to a single amino acid substitution (N-->D) immediately flanking the C-terminal anchor residue of the epitope. Proteasome-mediated digestion analysis of a synthetic 26-mer peptide derived from the Friend sequence shows that cleavage takes place predominantly C-terminal of D, instead of V as is the case for the Moloney MuLV sequence. Therefore, the C terminus of the epitope is not properly generated. Epitope-containing peptide fragments extended with an additional C-terminal D are not efficiently translocated by TAP and do not show significant binding affinity to MHC class I-Kb molecules. Thus, a potential CTL epitope present in the Friend virus sequence is not properly processed and presented because of a natural flanking aspartic acid that obliterates the correct C-terminal cleavage site. This constitutes a novel way to subvert proteasome-mediated generation of proper antigenic peptide fragments.

ATP-Binding Cassette Transporters↗
PubMed2001

Defined flanking spacers and enhanced proteolysis is essential for eradication of established tumors by an epitope string DNA vaccine.

Loss of immunogenic epitopes by tumors has urged the development of vaccines against multiple epitopes. Recombinant DNA technologies have opened the possibility to develop multiepitope vaccines in a relatively rapid and efficient way. We have constructed four naked DNA-based multiepitope vaccines, containing CTL, Th cell, and B cell epitopes of the human papillomavirus type 16. Here we show that gene gun-mediated vaccination with an epitope-based DNA vaccine protects 100% of the vaccinated mice against a lethal tumor challenge. The addition of spacers between the epitopes was crucial for the epitope-induced tumor protection, as the same DNA construct without spacers was significantly less effective and only protected 50% of the mice. When tested for therapeutic potential, only the epitope construct with defined spacers significantly reduced the size of established tumors, but failed to induce tumor regression. Only after targeting the vaccine-encoded protein to the protein degradation pathway by linking it to ubiquitin, the vaccine-induced T cell-mediated eradication of 100% of 7-day established tumors in mice. The finding that defined flanking sequences around epitopes and protein targeting dramatically increased the efficacy of epitope string DNA vaccines against established tumors will be of importance for the further development of multiepitope DNA vaccines toward clinical application.

Adjuvants, Immunologic↗
PubMed2002

A rational strategy to design multiepitope immunogens based on multiple Th lymphocyte epitopes.

Four HLA-DR-restricted HIV-derived Th lymphocyte (HTL) epitopes cross-reactive with the murine I-A(b) class II molecule were used to evaluate different vaccine design strategies to simultaneously induce multiple HTL responses. All four epitopes were immunogenic in H-2(b) mice, demonstrating the feasibility of murine models to evaluate epitope-based vaccines destined for human use. Immunization with a pool of peptides induced responses against all four epitopes; illustrating immunodominance does not prevent the induction of balanced multispecific responses. When different delivery systems were evaluated, a multiple Ag peptide construct was found to be less efficient than a linear polypeptide encompassing all four epitopes. Further characterization of linear polypeptide revealed that the sequential arrangement of the epitopes created a junctional epitope with high affinity class II binding. Disruption of this junctional epitope through the introduction of a GPGPG spacer restored the immunogenicity against all four epitopes. Finally, we demonstrate that a GPGPG spacer construct can be used to induce HTL responses by either polypeptide or DNA immunization, highlighting the flexibility of the approach.

Amino Acid Sequence↗
PubMed2003

Development of a DNA vaccine designed to induce cytotoxic T lymphocyte responses to multiple conserved epitopes in HIV-1.

Epitope-based vaccines designed to induce CTL responses specific for HIV-1 are being developed as a means for addressing vaccine potency and viral heterogeneity. We identified a set of 21 HLA-A2, HLA-A3, and HLA-B7 restricted supertype epitopes from conserved regions of HIV-1 to develop such a vaccine. Based on peptide-binding studies and phenotypic frequencies of HLA-A2, HLA-A3, and HLA-B7 allelic variants, these epitopes are predicted to be immunogenic in greater than 85% of individuals. Immunological recognition of all but one of the vaccine candidate epitopes was demonstrated by IFN-gamma ELISPOT assays in PBMC from HIV-1-infected subjects. The HLA supertypes of the subjects was a very strong predictor of epitope-specific responses, but some subjects responded to epitopes outside of the predicted HLA type. A DNA plasmid vaccine, EP HIV-1090, was designed to express the 21 CTL epitopes as a single Ag and tested for immunogenicity using HLA transgenic mice. Immunization of HLA transgenic mice with this vaccine was sufficient to induce CTL responses to multiple HIV-1 epitopes, comparable in magnitude to those induced by immunization with peptides. The CTL induced by the vaccine recognized target cells pulsed with peptide or cells transfected with HIV-1 env or gag genes. There was no indication of immunodominance, as the vaccine induced CTL responses specific for multiple epitopes in individual mice. These data indicate that the EP HIV-1090 DNA vaccine may be suitable for inducing relevant HIV-1-specific CTL responses in humans.

AIDS Vaccines↗
PubMed2006

Accumulation of CD8+ T cells in advanced-stage tumors and delay of disease progression following secondary immunization against an immunorecessive epitope.

Self-reactive T cells that survive the process of positive and negative selection during thymocyte development represent potential effector cells against tumors that express these same self-Ags. We have previously shown that CD8+ T lymphocytes (T(CD8)) specific for an immunorecessive epitope, designated epitope V, from the SV40 large T Ag (Tag) escape thymic deletion in line SV11 Tag-transgenic mice. In contrast, these mice are tolerant to the three most dominant Tag epitopes. The majority of the residual epitope V-specific T(CD8) have a low avidity for the target epitope, but a prime/boost regimen can expand higher avidity clones in vivo. Whether higher avidity T(CD8) targeting this epitope are affected by Tag-expressing tumors in the periphery or can be recruited for control of tumor progression remains unknown. In the current study, we determined the fate of naive TCR-transgenic T(CD8) specific for Tag epitope V (TCR-V cells) following transfer into SV11 mice bearing advanced-stage choroid plexus tumors. The results indicate that TCR-V cells are rapidly triggered by the endogenous Tag and acquire effector function, but fail to accumulate within the tumors. Primary immunization enhanced TCR-V cell frequency in the periphery and promoted entry into the brain, but a subsequent booster immunization caused a dramatic accumulation of TCR-V T cells within the tumors and inhibited tumor progression. These results indicate that epitope V provides a target for CD8+ T cells against spontaneous tumors in vivo, and suggests that epitopes with similar properties can be harnessed for tumor immunotherapy.

Adoptive Transfer↗
PubMed2006

Quantification of repertoire diversity of influenza-specific epitopes with predominant public or private TCR usage.

The H-2Db-restricted CD8 T cell immune response to influenza A is directed at two well-described epitopes, nucleoprotein 366 (NP366) and acid polymerase 224 (PA224). The responses to the two epitopes are very different. The epitope NP366-specific response is dominated by TCR clonotypes that are public (shared by most mice), whereas the epitope PA224-specific response is private (unique within each infected animal). In addition to being public, the NP366-specific response is dominated by a few clonotypes, when T cell clonotypes expressing the Vbeta8.3 element are analyzed. Herein, we show that this response is similarly public when the NP366+Vbeta4+ CD8 T cell response is analyzed. Furthermore, to determine whether these features resulted in differences in total TCR diversity in the NP366+ and PA224+ responses, we quantified the number of different CD8 T clonotypes responding to each epitope. We calculated that 50-550 clonotypes recognized each epitope in individual mice. Thus, although the character of the response to the two epitopes appeared to be different (private and diverse vs public and dominated by a few clonotypes), similar numbers of precursor cells responded to both epitopes and this number was of similar magnitude to that previously reported for other viral CD8 T cell epitopes. Therefore, even in CD8 T cell responses that appear to be oligoclonotypic, the total response is highly diverse.

Animals↗
PubMed1999

Molecular and functional analysis of a conserved CTL epitope in HIV-1 p24 recognized from a long-term nonprogressor: constraints on immune escape associated with targeting a sequence essential for viral replication.

It has been hypothesized that sequence variation within CTL epitopes leading to immune escape plays a role in the progression of HIV-1 infection. Only very limited data exist that address the influence of biologic characteristics of CTL epitopes on the emergence of immune escape variants and the efficiency of suppression HIV-1 by CTL. In this report, we studied the effects of HIV-1 CTL epitope sequence variation on HIV-1 replication. The highly conserved HLA-B14-restricted CTL epitope DRFYKTLRAE in HIV-1 p24 was examined, which had been defined as the immunodominant CTL epitope in a long-term nonprogressing individual. We generated a set of viral mutants on an HX10 background differing by a single conservative or nonconservative amino acid substitution at each of the P1 to P9 amino acid residues of the epitope. All of the nonconservative amino acid substitutions abolished viral infectivity and only 5 of 10 conservative changes yielded replication-competent virus. Recognition of these epitope sequence variants by CTL was tested using synthetic peptides. All mutations that abrogated CTL recognition strongly impaired viral replication, and all replication-competent viral variants were recognized by CTL, although some variants with a lower efficiency. Our data indicate that this CTL epitope is located within a viral sequence essential for viral replication. Targeting CTL epitopes within functionally important regions of the HIV-1 genome could limit the chance of immune evasion.

Animals↗
PubMed1999

Utilization of MHC class I transgenic mice for development of minigene DNA vaccines encoding multiple HLA-restricted CTL epitopes.

We engineered a multiepitope DNA minigene encoding nine dominant HLA-A2.1- and A11-restricted epitopes from the polymerase, envelope, and core proteins of hepatitis B virus and HIV, together with the PADRE (pan-DR epitope) universal Th cell epitope and an endoplasmic reticulum-translocating signal sequence. Immunization of HLA transgenic mice with this construct resulted in: 1) simultaneous CTL induction against all nine CTL epitopes despite their varying MHC binding affinities; 2) CTL responses that were equivalent in magnitude to those induced against a lipopeptide known be immunogenic in humans; 3) induction of memory CTLs up to 4 mo after a single DNA injection; 4) higher epitope-specific CTL responses than immunization with DNA encoding whole protein; and 5) a correlation between the immunogenicity of DNA-encoded epitopes in vivo and the in vitro responses of specific CTL lines against minigene DNA-transfected target cells. Examination of potential variables in minigene construct design revealed that removal of the PADRE Th cell epitope or the signal sequence, and changing the position of selected epitopes, affected the magnitude and frequency of CTL responses. Our results demonstrate the simultaneous induction of broad CTL responses in vivo against multiple dominant HLA-restricted epitopes using a minigene DNA vaccine and underline the utility of HLA transgenic mice in development and optimization of vaccine constructs for human use.

Amino Acid Sequence↗
PubMed1999

Conformational epitope of the type III group B Streptococcus capsular polysaccharide.

The protective epitope of the type III group B streptococcal polysaccharide (GBSPIII) is length dependent and conformational. To obtain a more accurate characterization of the conformational epitope, ELISA inhibition and surface plasmon resonance studies were conducted on two GBSPIII-specific mAbs using a large panel of oligosaccharide probes. The results of the studies confirmed that 2 repeating units (RU) is the minimum binding unit and that, while increases in chain length from 2 RU to 7 RU caused further optimization of the epitope, it remained monovalent. A 3-fold increase in affinity was observed between 7 RU and 20 RU, which, by surface plasmon resonance studies on a Fab, was shown to be due to both further optimization of the individual epitope and the occurrence of multivalency of epitope. The data support our hypothesis that the conformational epitope is an extended helical segment of the GBSPIII. GBSPIII exists mainly in the random coil form, which structurally mimics short oligosaccharide self Ags, but it can infrequently and spontaneously form extended helices. Although not prevalent in GBSPIII, the immune system preferentially selects these helical epitopes because they are unique to the polysaccharide. Contrary to a previously proposed model of GBSPIII binding in which the binding of the first Ab propagates a continuum of helical epitopes, our binding kinetics are consistent only with the helical epitope's being discontinuous and infrequent.

Animals↗
PubMed1999

Molecular configuration of Rh D epitopes as defined by site-directed mutagenesis and expression of mutant Rh constructs in K562 erythroleukemia cells.

The Rh D antigen is the most clinically important protein blood group antigen of the erythrocyte. It is expressed as a collection of at least 37 different epitopes. The external domains of the Rh D protein involved in epitope presentation have been predicted based on the analysis of variant Rh D protein structures inferred from their cDNA sequences and their D epitope expression. This analysis can never be absolute because (1) most partial D phenotypes involve multiple amino acid changes in the Rh D protein and (2) deficiency for 1 or more epitopes may be due to gross structural alteration in the variant Rh D protein structure. We report here the amino acid requirements for the majority of D epitopes. They have been defined by generating a series of novel Rh mutant constructs by mutagenesis using an Rh cE cDNA as template and mutagenic oligonucleotide primers. When transfected into K562 cells, the D epitope expression of the derived mutant clones was then assessed by flow cytometry. The introduction of 9 externally predicted Rh D-specific amino acids on the Rh cE protein was sufficient to express 80% of all tested D epitopes, whereas other clones expressed none. We concluded from our data that the D epitope expression is consistent with at least 6 different epitope clusters localized on external regions of the Rh D protein, most involving overlapping regions within external loops 3, 4, and 6.

Epitopes↗
PubMedDate not supplied

HIV neutralizing IgA in exposed seronegative subjects recognise an epitope within the gp41 coiled-coil pocket.

Human immunodeficiency virus (HIV)-specific IgA can be detected in cervical secretions, saliva, and sera of HIV-infected and HIV-uninfected individuals with a known exposure to the virus. IgA from HIV-uninfected exposed seronegative individuals (ESN) neutralize in vitro primary strains of HIV-1. We analyzed the epitopes of HIV recognized by serum HIV-specific IgA of ESN individuals to identify the antigenic correlates of HIV neutralization in exposed-uninfected subjects, and to verify whether different epitopes would be recognized by HIV-specific IgA of ESN and of HIV-infected patients. Results confirmed that HIV-neutralizing IgA are detected in sera of ESN and showed that neutralization of primary HIV strains is mediated by the recognition of different epitopes in HIV-infected patients and ESN. Thus, whereas IgA of HIV+ individuals recognize epitopes expressed both within gp120 and gp41, IgA of ESN exclusively bind to gp41-expressed epitopes. Epitope mapping revealed that the epitope recognized by serum IgA of ESN on gp41 is restricted to aa 581-584 (LQAR) and corresponds to coiled coil pocket in the alpha helic region. In contrast, the epitope seen by IgA of HIV-infected patients on gp41 is identified by two regions; the first is contained within the cystein loop (aa 589-618), the second correspond to C terminal region in the extra membrane region of gp 41 (aa 642-673). Thus, we have identified and characterized the epitopes that mediate neutralization of HIV in individuals in whom infection does not occur despite multiple exposures to the virus. These results have important implications for the development of a new therapy against HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Effects of the configuration of a multi-epitope chimeric malaria DNA vaccine on its antigenicity to mice.

OBJECTIVE: Four B and Th cell epitopes were selected from conservative domain of Plasmodium falciparum antigens to construct two groups of chimeric malaria DNA vaccines with different configurations and their antigenicities were studied. METHODS: The partially synthesized oligonucleotide was annealed, PCR amplified and cloned into a mammalian cell expression vector. By using a pair of isocaudamers on the vector, different single copies of B epitopes were multiplied and were tenderly stringed into two groups of chimeric DNA vaccine with different configurations. BALB/c mice were immunized with these DNA plasmids by either intramuscular or intradermal injections. RESULTS: The antisera from the immunized mice tested by ELISA showed that only the configuration which had a single copy of universal T helper cell epitope, CS. T3, located at the C terminal of the multi-copy B cell epitopes induced a high antibody response. The T helper cell epitope at any other position of the peptide, or the double T helper cell epitopes configured with the B cell epitopes did not enhance antibody response, and some configurations even decreased the humoral response to a B cell epitope. CONCLUSION: This study demonstrated that both combination and configuration of the epitope may affect the antigenicity of a chimeric multiple antigen.

Animals↗
PubMed2001

Endogenous expression and HLA stabilization assay of Plasmodium falciparum CTL epitope minigene in human HLA-A2. 1 and HLA-B51 cells.

OBJECTIVE: To evaluate the Plasmodium falciparum CTL epitope vaccines in HLA class I allele specific human cell lines that have high frequency among Chinese population. METHODS: Synthesized oligonucleotides encoding for P. f. CTL epitope genes, constructed eukaryotic expression plasmids, transfected the minigenes into HLA class I allele specific human cell lines and identified endogenous expressing of the minigenes by RT-PCR and HLA stabilization assay. RESULTS: Two mini-genes encoding Plasmodium falciparum CTL epitopes were designed and cloned, respectively, into an eukaryotic expressing vector to form TR26 which was restricted to HLA-B51, SH6 which was restricted to HLA-A2. 1, and TS, which had the two aforementioned mini-genes fused in tandem. All of these CTL epitope genes were transfected and endogenously expressed in respective cell lines containing appropriate HLA molecules. The obviously increased expressions of HLA class I molecules were detected in the transfected cell lines. It was demonstrated that the two discrete Plasmodium falciparum epitope genes were effectively processed and presented, and the close proximity of the two epitope genes in one chain as in mini-gene TS did not interfere with the processing and presenting of each epitope gene in corresponding cell line. CONCLUSION: A successful expression and presentation of multiple CTL epitope mini-gene in MHC class I allele specific human cell lines were demonstrated by an in vitro assay, which could be corresponding to the vaccination of CTL vaccines in people with different MHC I molecules. This work also suggested the possibility of constructing a multiple CTL epitope Plasmodium falciparum DNA vaccine that could cover most of Chinese population.

Animals↗
PubMed1992

Expression of tumor-associated epitopes on Epstein-Barr virus-immortalized B-cells and Burkitt's lymphomas transfected with epithelial mucin complementary DNA.

Mucins are among the best described human tumor-associated antigens. At least 73 tumor-reactive anti-mucin antibodies have been described; in addition, we have previously demonstrated the existence of tumor-specific cytotoxic T-lymphocyte epitopes on the mucin produced by breast and pancreatic tumors. To determine whether the appearance of tumor-associated mucin epitopes can be explained by altered post-translational modification of mucin in tumors, or whether the generation of these epitopes requires changes in the mucin gene itself, we studied four Burkitt's lymphomas and six Epstein-Barr virus-immortalized B-cell lines transfected with an expression construct containing the mucin complementary DNA. Transfected cell lines showed stable maintenance of the mucin gene, which comprises 20 or more tandem repeats of a 60-nucleotide sequence. Transfected cells expressed many tumor-associated mucin epitopes, suggesting that the changes in mucin synthesis seen in breast and pancreatic tumors are present in other malignant cell types as well. Furthermore, even though each cell line was transfected with the identical mucin construct, each expressed a different subset of tumor-associated mucin epitopes. This suggests that the specificity of these epitopes for tumors is not due to genetic alterations of the mucin gene in tumors. Incubating transfected cells with phenyl-N-acetyl-alpha-galactosaminide, an inhibitor of O-linked glycosylation, altered cell surface carbohydrate structures and resulted in increased expression of all tumor-associated epitopes, implicating incomplete glycosylation of mucin in the generation of these epitopes. These findings suggest that alterations in the posttranslational modification of normal gene products can result in the expression of novel epitopes. Furthermore, the ability to transfect cancer patients' Epstein-Barr virus-immortalized B-cell lines with mucin will provide an unlimited supply of autologous, mucin-bearing cells with which to study these patients' T-cell response to mucin.

Acetylgalactosamine↗
PubMed2003

Essential roles of tumor-derived helper T cell epitopes for an effective peptide-based tumor vaccine.

In this study, we identified a c-erbB-2/HER2/neu (HER2)-derived Th epitope (HER2 (16-30) ) and examined the role of Th epitopes in HER2-specific CD8+ T cell induction and in vivo tumor eradication, with a particular emphasis on the role of tumor cell-derived Th epitopes. Immunization of BALB/c mice using a mixture of Th epitope HER2 (16-30) and CTL epitope HER2 (63-71) administered subcutaneously with murine GM-CSF (mGM-CSF) induced a much higher level of HER2 (63-71) -specific CD8+ T cells compared with that obtained with the CTL epitope alone. HER2-unrelated OVA-derived Th epitope (OVA (323-339) ) exhibited a similar enhancing effect on HER2 (63-71) -specific CD8+ T cell induction. However, only mice immunized with HER2 (16-30) and HER2 (63-71), but not with a tumor-unrelated OVA (323-339) and HER2 (63-71), showed in vivo eradication of CMS5mHE tumor cells expressing HER2 but not OVA. This distinction was observed in preventative as well as therapeutic experimental settings. Conversely, both HER2 (16-30) and OVA (323-339) Th epitopes were equally effective in inducing the eradication of CMS5mHEOVA tumor cells which express HER2 as well as OVA. Our results clearly indicate that CTL and Th epitopes of target tumor cell origin should be used for effective induction of in vivo antitumor immunity.

Animals↗
PubMed1991

[Genetic, immunological and functional studies on lymphocytes with OKT4-epitope deficiency].

Although it is well-known that Leu3a-epitope on CD4 molecule functions as a receptor for human immunodeficiency virus (HIV), the function of OKT4-epitope is still obscure. In order to learn the significance of OKT4-epitope, we performed immunological and functional studies on lymphocytes obtained from individuals with incomplete/complete OKT-4 epitope deficiency. Their lymphocytes did not show any abnormality in their susceptibility to HIV infection, the internalization of CD4 molecules by TPA-treatment, the capability of producing IL-2 in vitro or the expression of IL-2R (alpha/beta-chain) by PHA-stimulation. By flow cytometric analysis it was demonstrated that quantity of OKT4-epitopes in the incomplete deficiency was approximately one-half less than that of normal individuals. Coupled with this fact and DNA analysis previously reported, individuals with incomplete/complete OKT4-epitope deficiency were considered to be heterozygote and homozygote, respectively. These results led us to the conclusion that OKT4-epitope deficiency was inherited as an autosomal codominant trait. Individuals with complete OKT4-epitope deficiency were found in 7 cases out of 1486 random samples (0.47%), from which individuals with incomplete OKT4-epitope deficiency were estimated to account for 12.8%.

Antibodies, Monoclonal↗