Abstract
We studied the polymorphisms of HLA-DR and HLA-DQ products from HLA-DRw13 haplotypes by analyzing the restriction of influenza A-specific cloned T cells from an HLA-DRw13,DQw1,Dw19 homozygous individual. The results show that (1) some functional epitopes, which can be borne by either HLA-DR or HLA-DQ molecules, are strictly correlated with the HLA-Dw19 subtype of HLA-DRw13. This clearly indicates that both HLA-DR and HLA-DQ products contribute to the HLA-Dw19 subdivision of HLA-DRw13. (2) At least two different restricting epitopes are borne by DR products: one is correlated with the HLA-DRwl3 serologically defined specificity, which includes Dw19 and Dw18 haplotypes; the other is correlated with the only HLA-Dw19 subtype of HLA-DRwl3. (3) Restricting epitopes borne by DQ molecules have been found on Dw19 cells only. (4) DQ-restricted clones were unable to react with DQwl APC of any other haplotypes tested, including DR1, DR2-long, DR2-short, and DRw14, demonstrating a high degree of functional polymorphism among the serologically defined DQw1 specificities.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- APC:
-
antigen-presenting cells
- cpm:
-
count per minute
- HAU:
-
hemagglutinin units
- IL-2:
-
interleukin 2
- MHC:
-
major histocompatibility complex
- mAb:
-
monoclonal antibody
- PBM:
-
peripheral blood mononuclear cells
- PHA:
-
phytohemagglutinin
- pl:
-
isoelectric point
- PMA:
-
phorbol myristic acetate
- SD:
-
standard deviation
References
Accola, R. S., Sekaly, R. P., McDonald, A. P., Corte, G., Gross, N., and Carrel, S.: Demonstration at the single cell level of the existence of distinct clusters of epitopes in two predefined human Ia molecular subsets. Eur. J. Immunol. 12: 166–169, 1982
Ball, E. J. and Stastny, P.: Antigen-specific HLA-restricted human T -cell lines. II. A GAT-specific Tcell line restricted by a determinant carried by an HLA-DQ molecule. Immunogenetics 20: 547–564, 1984
Barnstable, D. J., Bodmer, W. F., Brown, G., Galfre, G., Milstein, C., Williams, A. F., and Ziegler, A.: Production of monoclonal antibodies to group A erythrocyte HLA and other human cell surface antigens. New tools for genetic analysis. Cell 14: 9–14, 1978
Bodmer, J. and Bodmer, W.: Histocompatibility 1984. Immunol. Today 4: 251–254, 1984
Bono, R., Hyafil, F., Kahlil, J., Koblar, V., Wielo, J., Wollman, E., Mawas, C., and Fellous, M.: Monoclonal antibodies against HLADRw antigens. Transplant. Clin. Immunol. 11: 109–115, 1979
Bosch, M. L., Termijtelen, A., Gerrets, R., Schreuder, G. M. T., Bontrop, R. E., and Giphart, M. J.: Polymorphisms within the HLA-DRw6 haplotype. II. Protein charge heterogeneity reflects MLC subtyping of HLA-DRw6 homozygous cells. Immunogenetics 22: 23–33, 1985
Brodsky, F. M., Parham, P., and Bodmer, W. F.: Monoclonal antibodies to HLA-DRw determinants. Tissue Antigens 16: 30–33, 1980
Chen, Y. X., Evans, R., Pollack, M. S., Lanier, L. L., Phillips, J., Rousso, C., Werner, N. L., and Brodsky, F. M.: Characterization and expression of HLA-DC antigens defined by anti-Leu 10. Hum. Immunol. 10: 221–235, 1984
Corte, G., Calabi, F., Daniani, G., Bargellesi, A., Sorrentino, R., and Tosi, R.: Human Ia molecules carrying DC 1 determinants differ in both a and β subunits from Ia molecules carrying DR determinants. Nature 292: 357–360, 1981
Dupont, B., Braun, D. W., Yunis, E. J., and Carpenter, C. B.: HLA D by cellular typing. In P. I. Terasaki (ed.): Histocompatibility Testing, pp. 229–267, UCLA Tissue Typing Laboratory, Los Angeles, 1980
Eckels, D. D., Lamb, J. R., Lake, P., Woody, J. N., Johnson, A. H., and Hartzman, R. J.: Antigen-specific human T-lymphocyte clones. Genetic restriction of influenza virus-specific responses to HLA-D region genes. Hum. Immunol. 4: 313–324, 1982
Fleisher, B., Pawelec, G., and Wernet, P.: Homozygous typing cell-defined HLA-Dw specificities with restriction elements for influenza virusspecific proliferative human T lymphocyte clones. Hum. Immunol. 14: 37–47, 1985
Flomenberg, N., Knowles, R. W., Williams, D., Horibe, K., Rosenkrantz, K., and Dupont, B.: T lymphocyte clones detecting novel supertypic HLA class II allospecificities. Immunogenetics 22: 295–300, 1985
Haziot, A., Lepage, V., Freidel, A. C., Betuel, H., Degos, L., and Charron, D. J.: Biochemistry of HLA-DRw6: Evidence for seven distinct haplotypes. J. Immunol., in press, 1986
Hurley, C. K., Giles, R. C., and Capra, J. D.: The human MHC: Evidence for multiple HLA-D region genes. Immunol. Today 4: 219–225, 1983
Lamb, J. R., Eckels, D. D., Lake, P., Johnson, A. H., Hartzman, R. J., and Woody, J. N.: Antigen-specific human T lymphocyte clones: Induction, antigen specificity, and MHC restriction of influenza virus-immune clones. J. Immunol. 128: 233–238, 1982
Lampson, L. A. and Levy, R.: Two populations of Ia like molecules on a human B cell line. J. Immunol. 125: 293–299, 1980
Marti, G. E., Kuo, M. C., Shaw, C., Chang, C., DeMars, R., Sogu, J. A., Coligan, J. E., and Kindt, T. J.: A novel HLA-D/DR like antigen specific for human B lymphoid cells. Biochemical evidence for similarity to but nonidentity with known HLA-D/DR antigens. J. Exp. Med. 158: 1924–1937, 1983
Michon, J. M., Sterkers, G., Haziot, A., Freidel, A. C., Gebuhrer, L., Betuel, H., Gomard, E., Henin, Y., Lepage, V., Charron, D. J., and Levy, J. P.: Despite the lack of monospecific anti-DRw13 sera, a corresponding class II determinant can be defined by a DRw13 restricted anti-influenza virus T cell clone. Hum. Immunol. 15: 272–284, 1986
Ottenhoff, T. H. M., Elferink, D. G., Hermans, J., and de Vries, R. R. P.: HLA class II restriction repertoire of antigen-specific T cells. I. The main restriction determinants for antigen presentation are associated with HLA-D/DR and not with DP and DQ. Hum. Immunol. 13: 105–116, 1985
Reinsmoen, N. L., Sazazuki, T., Kaneoka, H., Ohta, N., Noreen, H. J., Greenberg, L., and Kersey, J. H.: Two distinct HLA-D specificities (DHO and Dw2) in linkage with HLA-DRw2 as defined in white and Japanese populations. Transplant. Proc. 10: 789–791, 1979
Schreuder, G. M. T., Parleoliet, J., Termijtelen, A., and Van Rood, J. J.: Reanalysis of the HLA-DRw6 complex. Tissue Antigens 21: 62–74, 1983
Shackelford, D. A., Eibl, B., and Strominger, J. L.: Structural polymorphism of the DC 1 light chains from DR I-, DR2-, and DRw6-positive cell lines. Immunogenetics 18: 625–637, 1983
Sterkers, G., Henin, Y., Lepage, V., Fradellizi, C., Hannoun, C., and Levy, J. P.: Influenza A hemagglutinin specific T cell clones strictly restricted by HLA-DR1 or HLA-DR7 molecules. Eur. J. Immunol. 14: 125–132, 1984
Sterkers, G., Michon, J., Henin, Y., Gomard, E., Hannoun, C., and Levy, J. P.: Fine specificity analysis of human influenza-specific cloned cell lines. Cell. Immunol. 94: 394–405, 1985
Termijtelen, A., Schreuder, G. M. T., Mickelson, E. M., and Van Rood, J. J.: Ninth International Histocompatibility Workshop pretesting of Dw6 HTCS: Two subtypes of Dw6. Tissue Antigens 24: 10–17, 1984
Watson, A. J., DeMars, R., Trowbridge, I. S., and Bach, J. H.: Detection of a novel human class II HLA antigen. Nature 304: 358–361, 1983
WHO Nomenclature Report 1984: Nomenclature for factors of the HLA system 1984. Tissue Antigens 24: 73–80, 1984
Zeliszewski, D., Sterkers, G., Freidel, C., Gebuhrer, L., Betuel, H., and Levy, J. P.: Functional definition of HLA-DR and -DQ epitopes specific for DR2-short, DwFJO haplotype. Immunogenetics 23: 385–392, 1986
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Michon, J., Henin, Y., Sterkers, G. et al. Highly polymorphic products of both HLA-DR and HLA-DQ genes contribute to the polymorphism of the HLA-DR w13 haplotype. Immunogenetics 24, 177–183 (1986). https://doi.org/10.1007/BF00364746
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00364746