Abstract
Activation of T lymphocytes by immunogenic peptides bound to HLA molecules is a central event in the generation of an immune response. To determine the sites on HLA molecules involved in this process, we isolated mutant EBV-transformed B cell clones that express altered HLA- DR3 molecules. One mutant has lost the ability to stimulate a T cell clone specific for a mycobacterial protein, but retains the ability to stimulate other antigen-specific T cells. The DNA sequence of the complete DR alpha and beta coding regions revealed a single nucleotide change resulting in a glutamic acid to lysine substitution at amino acid 9 in the first hypervariable region of the DR beta chain. These results are discussed in relation to a recently proposed model of class II molecule structure.
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Selected References
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- Babbitt B. P., Allen P. M., Matsueda G., Haber E., Unanue E. R. Binding of immunogenic peptides to Ia histocompatibility molecules. 1985 Sep 26-Oct 2Nature. 317(6035):359–361. doi: 10.1038/317359a0. [DOI] [PubMed] [Google Scholar]
- Bell J. I., Denney D., Jr, Foster L., Belt T., Todd J. A., McDevitt H. O. Allelic variation in the DR subregion of the human major histocompatibility complex. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6234–6238. doi: 10.1073/pnas.84.17.6234. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987 Oct 8;329(6139):512–518. doi: 10.1038/329512a0. [DOI] [PubMed] [Google Scholar]
- Brown J. H., Jardetzky T., Saper M. A., Samraoui B., Bjorkman P. J., Wiley D. C. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature. 1988 Apr 28;332(6167):845–850. doi: 10.1038/332845a0. [DOI] [PubMed] [Google Scholar]
- Johnson J. P., Meo T., Riethmüller G., Schendel D. J., Wank R. Direct demonstration of an HLA-DR allotypic determinant on the low molecular weight (beta) subunit using a mouse monoclonal antibody specific for DR3. J Exp Med. 1982 Jul 1;156(1):104–111. doi: 10.1084/jem.156.1.104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koning F., Schreuder I., Giphart M., Bruning H. A mouse monoclonal antibody detecting a DR-related MT2-like specificity: serology and biochemistry. Hum Immunol. 1984 Apr;9(4):221–230. doi: 10.1016/0198-8859(84)90027-2. [DOI] [PubMed] [Google Scholar]
- Levine F., Erlich H., Mach B., Leach R., White R., Pious D. Deletion mapping of HLA and chromosome 6p genes. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3741–3745. doi: 10.1073/pnas.82.11.3741. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mellins E., Woelfel M., Pious D. Importance of HLA-DQ and -DP restriction elements in T-cell responses to soluble antigens: mutational analysis. Hum Immunol. 1987 Mar;18(3):211–223. doi: 10.1016/0198-8859(87)90086-3. [DOI] [PubMed] [Google Scholar]
- Pious D., Dixon L., Levine F., Cotner T., Johnson R. HLA class II regulation and structure. Analysis with HLA-DR3 and HLA-DP point mutants. J Exp Med. 1985 Oct 1;162(4):1193–1207. doi: 10.1084/jem.162.4.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sachs J. A., Fernandez N., Kurpisz M., Okoye R., Ogilvie J., Awad J., Labeta M., Festenstein H. Serological biochemical and functional characterisation of three different HLA-DR monoclonal antibodies derived from C57BL6 mice. Tissue Antigens. 1986 Oct;28(4):199–207. doi: 10.1111/j.1399-0039.1986.tb00483.x. [DOI] [PubMed] [Google Scholar]
- Schamboeck A., Korman A. J., Kamb A., Strominger J. L. Organization of the transcriptional unit of a human class II histocompatibility antigen: HLA-DR heavy chain. Nucleic Acids Res. 1983 Dec 20;11(24):8663–8675. doi: 10.1093/nar/11.24.8663. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shimonkevitz R., Kappler J., Marrack P., Grey H. Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing. J Exp Med. 1983 Aug 1;158(2):303–316. doi: 10.1084/jem.158.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wong C., Dowling C. E., Saiki R. K., Higuchi R. G., Erlich H. A., Kazazian H. H., Jr Characterization of beta-thalassaemia mutations using direct genomic sequencing of amplified single copy DNA. 1987 Nov 26-Dec 2Nature. 330(6146):384–386. doi: 10.1038/330384a0. [DOI] [PubMed] [Google Scholar]