Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1987 Feb 1;165(2):428–443. doi: 10.1084/jem.165.2.428

Alloreactive cytolytic T cell clones with dual recognition of HLA-B27 and HLA-DR2 antigens. Selective involvement of CD8 in their class I-- directed cytotoxicity

PMCID: PMC2188505  PMID: 3102669

Abstract

HLA-B27- responder cells were stimulated in vitro with HLA-B27.1+ lymphoblastoid cell lines, and alloreactive CTL clones were obtained by limiting dilution. Three of these clones specifically lysed B27.1+ targets. In addition, they also lysed homozygous DR2 targets with various degrees of efficiency, depending on the Dw specificity of the target cell. All three clones possessed a homogeneous CD3+,CD8+,CD4- phenotype and were also homogeneous upon subcloning. Cold-target inhibition analyses showed mutual inhibition of B27.1 target lysis by DR2 targets and vice versa. Lysis of B27.1 targets was selectively inhibited by anti-class I mAbs. In contrast, lysis of DR2 targets was inhibited only by anti-class II and anti-DR monomorphic antibodies, but not by anti-class I, anti-DQw1, or anti-DP antibodies. The results indicate that these clones display dual recognition for HLA-B27.1 and for HLA-DR2 and suggest that HLA-B27.1 may share at least one epitope that is closely related to some stimulatory Dw determinants present on the HLA-DR2 antigens. Lysis of both B27+ and DR+ targets was inhibited by an anti-CD3 mAb. In contrast, an anti-CD8 antibody selectively inhibited the B27- but not the DR2-directed killing by these clones. The data support a stabilizing role of CD8 through its binding to the same class I (but not class II) molecule on the target cell bound by the T cell antigen receptor.

Full Text

The Full Text of this article is available as a PDF (960.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Acuto O., Hussey R. E., Reinherz E. L. Multiple class I and class II major histocompatibility complex allospecificities are generated with T cell receptor variable (V) domains created by a single Ti beta V gene family. J Exp Med. 1985 Oct 1;162(4):1387–1392. doi: 10.1084/jem.162.4.1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aparicio P., Vega M. A., López de Castro J. A. One allogeneic cytolytic T lymphocyte clone distinguishes three different HLA-B27 subtypes: identification of amino acid residues influencing the specificity and avidity of recognition. J Immunol. 1985 Nov;135(5):3074–3081. [PubMed] [Google Scholar]
  3. Bank I., Chess L. Perturbation of the T4 molecule transmits a negative signal to T cells. J Exp Med. 1985 Oct 1;162(4):1294–1303. doi: 10.1084/jem.162.4.1294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barnstable C. J., Bodmer W. F., Brown G., Galfre G., Milstein C., Williams A. F., Ziegler A. Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis. Cell. 1978 May;14(1):9–20. doi: 10.1016/0092-8674(78)90296-9. [DOI] [PubMed] [Google Scholar]
  5. Biddison W. E., Rao P. E., Talle M. A., Goldstein G., Shaw S. Possible involvement of the T4 molecule in T cell recognition of class II HLA antigens. Evidence from studies of CTL-target cell binding. J Exp Med. 1984 Mar 1;159(3):783–797. doi: 10.1084/jem.159.3.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brodsky F. M., Parham P., Bodmer W. F. Monoclonal antibodies to HLA--DRw determinants. Tissue Antigens. 1980 Jul;16(1):30–48. doi: 10.1111/j.1399-0039.1980.tb00285.x. [DOI] [PubMed] [Google Scholar]
  7. Colombani J., Lepage V., Kalil J. HLA monoclonal antibody registry: second listing. Tissue Antigens. 1983 Aug;22(2):97–106. doi: 10.1111/j.1399-0039.1983.tb01175.x. [DOI] [PubMed] [Google Scholar]
  8. Dembić Z., Haas W., Weiss S., McCubrey J., Kiefer H., von Boehmer H., Steinmetz M. Transfer of specificity by murine alpha and beta T-cell receptor genes. Nature. 1986 Mar 20;320(6059):232–238. doi: 10.1038/320232a0. [DOI] [PubMed] [Google Scholar]
  9. Ellis S. A., Taylor C., McMichael A. Recognition of HLA-B27 and related antigen by a monoclonal antibody. Hum Immunol. 1982 Aug;5(1):49–59. doi: 10.1016/0198-8859(82)90030-1. [DOI] [PubMed] [Google Scholar]
  10. Fazekas de St Groth B., Gallagher P. F., Miller J. F. Involvement of Lyt-2 and L3T4 in activation of hapten-specific Lyt-2+ L3T4+ T-cell clones. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2594–2598. doi: 10.1073/pnas.83.8.2594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fleischer B., Schrezenmeier H., Wagner H. Function of the CD4 and CD8 molecules on human cytotoxic T lymphocytes: regulation of T cell triggering. J Immunol. 1986 Mar 1;136(5):1625–1628. [PubMed] [Google Scholar]
  12. Garman R. D., Ko J. L., Vulpe C. D., Raulet D. H. T-cell receptor variable region gene usage in T-cell populations. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3987–3991. doi: 10.1073/pnas.83.11.3987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gaston J. S., Rickinson A. B., Epstein M. A. Cross-reactivity of self-HLA-restricted Epstein-Barr virus-specific cytotoxic T lymphocytes for allo-HLA determinants. J Exp Med. 1983 Dec 1;158(6):1804–1821. doi: 10.1084/jem.158.6.1804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Krangel M. S., Biddison W. E., Strominger J. L. Comparative structural analysis of HLA-A2 antigens distinguishable by cytotoxic T lymphocytes. II. Variant DK1: evidence for a discrete CTL recognition region. J Immunol. 1983 Apr;130(4):1856–1862. [PubMed] [Google Scholar]
  15. Krangel M. S., Taketani S., Biddison W. E., Strong D. M., Strominger J. L. Comparative structural analysis of HLA-A2 antigens distinguishable by cytotoxic T lymphocytes: variants M7 and DR1. Biochemistry. 1982 Nov 23;21(24):6313–6321. doi: 10.1021/bi00267a042. [DOI] [PubMed] [Google Scholar]
  16. Krensky A. M., Clayberger C., Greenstein J. L., Crimmins M., Burakoff S. J. A DC-specific cytolytic T lymphocyte line is OKT8+1. J Immunol. 1983 Dec;131(6):2777–2780. [PubMed] [Google Scholar]
  17. Lamoyi E., Nisonoff A. Preparation of F(ab')2 fragments from mouse IgG of various subclasses. J Immunol Methods. 1983 Jan 28;56(2):235–243. doi: 10.1016/0022-1759(83)90415-5. [DOI] [PubMed] [Google Scholar]
  18. Lampson L. A., Levy R. Two populations of Ia-like molecules on a human B cell line. J Immunol. 1980 Jul;125(1):293–299. [PubMed] [Google Scholar]
  19. Landegren U., Ramstedt U., Axberg I., Ullberg M., Jondal M., Wigzell H. Selective inhibition of human T cell cytotoxicity at levels of target recognition or initiation of lysis by monoclonal OKT3 and Leu-2a antibodies. J Exp Med. 1982 May 1;155(5):1579–1584. doi: 10.1084/jem.155.5.1579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. MacDonald H. R., Glasebrook A. L., Bron C., Kelso A., Cerottini J. C. Clonal heterogeneity in the functional requirement for Lyt-2/3 molecules on cytolytic T lymphocytes (CTL): possible implications for the affinity of CTL antigen receptors. Immunol Rev. 1982;68:89–115. doi: 10.1111/j.1600-065x.1982.tb01061.x. [DOI] [PubMed] [Google Scholar]
  21. Malissen B., Rebai N., Liabeuf A., Mawas C. Human cytotoxic T cell structures associated with expression of cytolysis. I. Analysis at the clonal cell level of the cytolysis-inhibiting effect of 7 monoclonal antibodies. Eur J Immunol. 1982 Sep;12(9):739–747. doi: 10.1002/eji.1830120908. [DOI] [PubMed] [Google Scholar]
  22. Meuer S. C., Schlossman S. F., Reinherz E. L. Clonal analysis of human cytotoxic T lymphocytes: T4+ and T8+ effector T cells recognize products of different major histocompatibility complex regions. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4395–4399. doi: 10.1073/pnas.79.14.4395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Moretta A., Pantaleo G., Mingari M. C., Moretta L., Cerottini J. C. Clonal heterogeneity in the requirement for T3, T4, and T8 molecules in human cytolytic T lymphocyte function. J Exp Med. 1984 Mar 1;159(3):921–934. doi: 10.1084/jem.159.3.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nathenson S. G., Geliebter J., Pfaffenbach G. M., Zeff R. A. Murine major histocompatibility complex class-I mutants: molecular analysis and structure-function implications. Annu Rev Immunol. 1986;4:471–502. doi: 10.1146/annurev.iy.04.040186.002351. [DOI] [PubMed] [Google Scholar]
  25. Nepom G. T., Nepom B. S., Wilson M. E., Mickelson E., Antonelli P., Hansen J. A. Multiple Ia-like molecules characterize HLA-DR2-associated haplotypes which differ in HLA-D. Hum Immunol. 1984 Jul;10(3):143–151. doi: 10.1016/0198-8859(84)90035-1. [DOI] [PubMed] [Google Scholar]
  26. Pierres A., Naquet P., Van Agthoven A., Bekkhoucha F., Denizot F., Mishal Z., Schmitt-Verhulst A. M., Pierres M. A rat anti-mouse T4 monoclonal antibody (H129.19) inhibits the proliferation of Ia-reactive T cell clones and delineates two phenotypically distinct (T4+, Lyt-2,3-, and T4-, Lyt-2,3+) subsets among anti-Ia cytolytic T cell clones. J Immunol. 1984 Jun;132(6):2775–2782. [PubMed] [Google Scholar]
  27. Platsoucas C. D. Human T cell antigens involved in cytotoxicity against allogeneic or autologous chemically modified targets. Association of the Leu 2a/T8 antigen with effector-target cell binding and of the T3/Leu 4 antigen with triggering. Eur J Immunol. 1984 Jun;14(6):566–577. doi: 10.1002/eji.1830140615. [DOI] [PubMed] [Google Scholar]
  28. Reinsmoen N. L., Layrisse Z., Betuel H., Freidel A. C., Bach F. H. A study of HLA-DR2 associated HLA-Dw/LD specificities. Hum Immunol. 1984 Oct;11(2):105–115. doi: 10.1016/0198-8859(84)90049-1. [DOI] [PubMed] [Google Scholar]
  29. Schilham M. W., Lang R., Benner R., Zinkernagel R. M., Hengartner H. Characterization of an Lyt-2+ alloreactive cytotoxic T cell clone specific for H-2Db that cross-reacts with I-Ek. J Immunol. 1986 Nov 1;137(9):2748–2754. [PubMed] [Google Scholar]
  30. Shaw S., Goldstein G., Springer T. A., Biddison W. E. Susceptibility of cytotoxic T lymphocyte (CTL) clones to inhibition by anti-T3 and anti-T4 (but not anti-LFA-1) monoclonal antibodies varies with the "avidity" of CTL-target interaction. J Immunol. 1985 May;134(5):3019–3026. [PubMed] [Google Scholar]
  31. Sone T., Tsukamoto K., Hirayama K., Nishimura Y., Takenouchi T., Aizawa M., Sasazuki T. Two distinct class II molecules encoded by the genes within HLA-DR subregion of HLA-Dw2 and Dw12 can act as stimulating and restriction molecules. J Immunol. 1985 Aug;135(2):1288–1298. [PubMed] [Google Scholar]
  32. Swain S. L. T cell subsets and the recognition of MHC class. Immunol Rev. 1983;74:129–142. doi: 10.1111/j.1600-065x.1983.tb01087.x. [DOI] [PubMed] [Google Scholar]
  33. Vega M. A., Ezquerra A., Rojo S., Aparicio P., Bragado R., López de Castro J. A. Structural analysis of an HLA-B27 functional variant: identification of residues that contribute to the specificity of recognition by cytolytic T lymphocytes. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7394–7398. doi: 10.1073/pnas.82.21.7394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Vega M. A., Wallace L., Rojo S., Bragado R., Aparicio P., López de Castro J. A. Delineation of functional sites in HLA-B27 antigens. Molecular analysis of HLA-B27 variant Wewak I defined by cytolytic T lymphocytes. J Immunol. 1985 Nov;135(5):3323–3332. [PubMed] [Google Scholar]
  35. Watson A. J., DeMars R., Trowbridge I. S., Bach F. H. Detection of a novel human class II HLA antigen. 1983 Jul 28-Aug 3Nature. 304(5924):358–361. doi: 10.1038/304358a0. [DOI] [PubMed] [Google Scholar]
  36. de Vries J. E., Spits H. Cloned human cytotoxic T lymphocyte (CTL) lines reactive with autologous melanoma cells. I. In vitro generation, isolation, and analysis to phenotype and specificity. J Immunol. 1984 Jan;132(1):510–519. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES