Skip to main content
SpringerLink
Log in

HLA class l specific t lymphocyte clones with dual alloreactive functions

  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

Four human T lymphocyte clones exhibiting proliferative responses to class I HLA antigens were isolated from an in vitro mixed lymphocyte culture (MLC). Three clones expressed the Leu-2+3− phenotype and demonstrated proliferation in response to HLA-B8, while the fourth clone expressed the Leu-2−3+ phenotype and proliferated in response to HLA-A2. These clones were also cytotoxic towards cells bearing the same target antigens. Blocking studies utilizing monoclonal antibodies demonstrated that proliferation was triggered by determinants on the class I molecule itself, and these determinants appear to be spatially close to those which determine serologic allospecificity. These findings support the concept that the class I molecules themselves are the weak MLC stimulating determinants previously mapped to the HLA-A and B regions of the major histocompatibility complex.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

B-LCL:

B-lymphoblastoid cell line

cpm:

counts per minute

FCS:

fetal calf serum

HS:

human serum

3H-TdR:

tritiated thymidine

IL-2:

interleukin-2

IL2-CM:

interleukin-2 containing conditioned medium

MHC:

major histocompatibility complex

MLC:

mixed lymphocyte culture

MoAb:

monoclonal antibody

PBL:

peripheral blood mononuclear leukocytes

PLT:

primed lymphocyte test

References

  • Allison, J. P., Belvedere, M., Reisfeld, R. A., Pellegrino, M. A., and Ferrone, S.: Serological and immunochemical characterization of HLA-A9 xenoantisera. J. Immunol. 121: 579–585, 1978

    Google Scholar 

  • Bach, F. H., Widmer, M. B., Bach, M. L., and Klein, J.: Serologically defined and lymphocyte-defined components of the major histocompatibility complex in the mouse. J. Exp. Med. 136: 1430–1444, 1972

    Google Scholar 

  • Bach, F. H., Alter, B. J., Widmer, M. B., Segall, M., and Dunlap, B.: Cloned cytotoxic and non-cytotoxic lymphocytes in mouse and man. Immunol. Rev. 54: 5–26, 1981

    Google Scholar 

  • Bijnen, A. B., Schreuder, I., Volkers, W. S., Parlevliet, J., and van Rood, J. J.: The lymphocyte activating influence of the HLA-A region. Immunogenetics 4: 1–5, 1977

    Google Scholar 

  • Dupont, B., Good, R. A., Hansen, G. S., Jersild, C., Nielsen, L. S., Park, B. H., Svejgaard, A., Thomsen, M., and Yunis, E. J.: Two separate genes controlling stimulation in mixed lymphocyte reaction in man. Proc. Natl. Acad. Sci. U.S.A. 71: 52–56, 1974

    Google Scholar 

  • Eijsvoogel, V. P., van Rood, J. J., Du Bois, M. J. G. J., and Schellekens, P. T. A.: Position of a locus determining mixed lymphocyte reaction distinct from the known HL-Aloci. Eur. J. Immunol. 2: 413–421, 1972

    Google Scholar 

  • Engleman, E.G., Benike, C. J.; Grumet, C., and Evans, R. L.: Activation of human T lymphocyte subsets: helper and suppressor/cytotoxic cells recognize and respond to distinct histocompatibility antigens. J. Immunol. 127: 2124–2129, 1981

    Google Scholar 

  • Evans, R. L., Wall, D. W., Platsoucas, C. D., Siegal, F. P., Fikrig, S. M., Testa, C. M., and Good, R. A.: Thymus-dependent membrane antigens in man: inhibition of cell mediated lympholysis by monoclonal antibodies to TH2 antigen. Proc. Natl. Acad. Sci. U.S.A. 78: 544–548, 1981

    Google Scholar 

  • Fathman, C. G. and Kimoto, M.: Studies utilizing murine T cell clones: Ir genes, la antigens, and MLR stimulating determinants. Immunol. Rev. 54: 57–80, 1981

    Google Scholar 

  • Festenstein, H. and Démant, P.: Workshop summary of genetic determinants of cell-mediated immune reactions in the mouse. Transplant. Proc. 4: 1321–1327, 1973

    Google Scholar 

  • Flomenberg, N., Duffy, E., Naito, K., and Dupont, B.: Two distinct phenotypes of HLA-DR specific cytotoxic T-cell lines. Immunogenetics 17: 317–324, 1983a

    Google Scholar 

  • Flomenberg, N., Naito, K., Duffy, E., Knowles, R. W., Evans, R. L., and Dupont, B. Allocytotoxic T-cell clones: both Lea 2+3− and Len 2−3+ T cells recognize class I histocompatibility antigens. Eur. J. Immunol. in press, 1983b

  • Forman, J. and Klein, J.: Analysis of H-2 mutants: evidence for multiple CML target specificities controlled by the H-2 K b gene. Immunogenetics 1: 469–481, 1975

    Google Scholar 

  • Gillis, S. and Watson, J.: Interleukin-2 dependent culture of cytolytic T-cell lines. Immunol. Rev. 54: 81–110, 1981

    Google Scholar 

  • Glasebrook, A. L. and Fitch, F. W.: T-cell lines which cooperate in generation of specific cytolytic activity. Nature 278: 171–173, 1979a

    Google Scholar 

  • Glasebrook, A. L. and Fitch, F. W.: Alloreactive cloned T-cell lines. I. Interactions between cloned amplifier and cytolytic T-cell lines. J. Exp. Med. 151: 876–895, 1979b

    Google Scholar 

  • Glasebrook, A. L. and MacDonald, H. R.: Monoclonal anti-Lyt-2 antibodies block the activation of cytolytic T lymphocyte precursors. J. Immunol. 130: 1552–1555, 1983

    Google Scholar 

  • Hansen, J. A., Fu, S. M., Antonelli, P., Kamoun, M., and Kunkel, H. G.: B-lymphoid cell lines derived from HLA-D homozygous donors. Immunogenetics 8: 51–64, 1979

    Google Scholar 

  • Johnson, A. H., Amos, D. B., Noreen, H., and Yunis, E. J.: Strong mixed lymphocyte reaction associated with the LA or first locus HL-A. Transplantation 20: 291–295, 1975

    Google Scholar 

  • Klein, J., Widmer, M. B., Segall, M., and Bach, F. H.: Mixed lymphocyte culture reactivity and H-2 histocompatibility loci differences. Cellular Immunity 4: 442–446, 1972

    Google Scholar 

  • Klein, J., Hauptfeld, M., and Hauptfeld, V.: Evidence for a third, Ir-associated histocompatibility region in the H-2 complex of the mouse. Immunogenetics 1: 45–56, 1974

    Google Scholar 

  • Klein, J., Juretic, A., Baxevanis, C. N., and Nagy, Z. A.: The traditional and a new version of the mouse H-2 complex. Nature 291: 455–460, 1981

    Google Scholar 

  • Kornbluth, J., Silver, D. M., and Dupont, B.: Cloning and characterization of primary alloreactive human T-lymphocytes. Immunol. Rev. 54: 111–154, 1981

    Google Scholar 

  • Lefkovits, I. and Waldmann, H.: Clone size estimation. In I. Lefkovits and H. Waldmann (eds.): Limiting dilution analysis of cells in the immune system, pp. 83–93, Cambridge University Press, Cambridge, London, New York, Melbourne, 1979

    Google Scholar 

  • Lonai, P. and McDevitt, H. O.: The expression of I-region gene products on lymphocytes. II. Genetic localization and cellular distribution of MLR determinants. Immunogenetics 4: 33–55, 1977

    Google Scholar 

  • Meo, T., Vives, G., Rijnbeek, A. M., Miggiano, V. C., Nabholz, M., and Shreffler, D. C.: A bipartite interpretation and tentative mapping of H-2 associated MLR determinants in the mouse. Transplant. Proc. 4: 1339–1350, 1973

    Google Scholar 

  • Pellegrino, M. A., Ferrone, S., and Pellegrino, A.: A simple microabsorption technique for HLA typing. Proc. Soc. Exp. Biol. Med. 139: 484–488, 1972

    Google Scholar 

  • Pellegrino, M. A., Belvedere, M., Pellegrino, A. G., and Ferrone, S.: B peripheral lymphocytes express more HLA antigens than T peripheral lymphocytes. Transplantation 29: 93–95, 1978

    Google Scholar 

  • Pellegrino, M. A., Ng, A. K., Russo, C., Glassy, M., and Ferrone, S.: Immunochemical analysis of anti-HLA-A2, HLA-A3, and HLA-B27 xenoantisera elicited with hybrids between human and murine cells. Immunogenetics 14: 141–152, 1981

    Google Scholar 

  • Roopenian, D. C., Widmer, M. B., Orosz, C. G., and Bach, F. H.: Helper cell-independent cytolytic T-lymphocytes specific for a minor histocompatibility antigen. J. Immunol. 130: 542–545, 1983

    Google Scholar 

  • Russo, C., Pellegrino, M. A., Ng, A. K., Wilson, B. S., and Ferrone, S.: Antigenic constitution of HLA-A, B, C molecules: Immunochemical analysis with monoclonal xenoantibodies. In S. Ferrone and B. G. Solheim (eds.): HLA Typing: Methodology and Clinical Aspects, Vol. l, pp. 77–100, CRC press, Boca Raton, 1982

    Google Scholar 

  • Russo, C., Ng, A. K., Pellegrino, M. A., and Ferrone, S.: The monoclonal antibody CR11-351 discriminates HLA-A2 variants identified by T cells. Immunogenetics 18: 23–35, 1983

    Google Scholar 

  • Schendel, D.J., Wank, R., and Dupont, B.: Standardization of the human in vitro cell-mediated lympholysis technique. Tissue Antigens 13: 112–120, 1979

    Google Scholar 

  • Sheehy, M. J. and Bach, F. H.: Primed LD typing (PLT) technical considerations. Tissue Antigens 8: 157–171, 1976

    Google Scholar 

  • Sredni, B. and Schwartz, R. H.: Antigen specific, proliferating, T-lymphocyte clones. Methodology, specificity, MHC restriction and alloreactivity. Immunol. Rev. 54: 187–224, 1981

    Google Scholar 

  • Suciu-Foca, N. and Rubinstein, P.: Genetic fine structure of the HLA region. Transplant. Proc. 9: 385–391, 1977

    Google Scholar 

  • Termitjelen, A. and van Rood, J. J.: Complexity of stimulation in MLC and the influence of matching for HLA-A and -B. Scand. J. Immunol. 14: 459–466, 1981

    Google Scholar 

  • Termitjelen, A., Bradley, B. A., and van Rood, J. J.: The influence of HLA-A and -B associated gene products on typing for HLA-D by the HTC and PLT methods. Tissue Antigens 10: 161, 1977

    Google Scholar 

  • Thorsby, E., Hirschberg, H., and Helgessen, A.: A second locus determinant human MLC response: Separate lymphocyte populations recognize the products of each reference MLC-locus allele in allogencic combinations. Transplant. Proc. 5: 1513–1518, 1973

    Google Scholar 

  • von Boehmer, H. and Haas, W.: H-2 restricted cytolytic and noncytolytic T-cell clones: Isolation, specificity and functional analysis. Immunol. Rev. 54: 27–56, 1981

    Google Scholar 

  • von Boehmer, H. and Turton, K.: Autonomously proliferating K/D-restricted cytolytic T cell clones. Eur. J. Immunol. 13 : 176–179, 1983

    Google Scholar 

  • Wank, R., Schendel, D. J., Hansen, J. A., Yunis, E. J., and Dupont, B.: Two different HLA restimulating determinants separated by recombination and titration. Third annual meeting of the AACHT, New Orleans, 1977. Transplant. Proc. 9: 1771–1775, 1977

    Google Scholar 

  • Wank, R., Schendel, D. J., Blanco, M. E., and Dupont, B.: Secondary MLC responses of primed lymphocytes after selective sensitization to non-HLA-D determinants. Scand. J. Immunol. 9: 499–505, 1979

    Google Scholar 

  • Wee, S. L., Chen, L. K., Strassman, G., and Bach, F. H.: Helper cell-independent cytotoxic clones in man. J. Exp. Med. 156: 1854–1859, 1982

    Google Scholar 

  • Widmer, M. B. and Bach, F. H.: Antigen-driven helper cell-independent cloned cytolytic T lymphocytes. Nature 294: 750–752, 1981

    Google Scholar 

  • Yunis, E. J. and Amos, D. B.: Three closely linked genetic systems relevant to transplantation. Proc. Natl. Acad. Sci. U.S.A. 68: 3031–3035, 1971

    Google Scholar 

  • Zeevi, A., Scheffel, C., Anne, K., and Duquesnoy, R. J.: Primed lymphocyte testing specificity of alloreactive lymphocyte clones for HLA-B locus determinants. Proc. Natl. Acad. Sci. U.S.A. 80: 1440–1444, 1983

    Google Scholar 

  • Zier, K. S., Gross-Wilde, H., Huber, C., Braunstein, H., and Albert, E. D.: Restimulation in secondary MLC by a non-D-locus determinant within the MHC. Immunogenetics 6: 459–469, 1978

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Human Immunogenetics, Memorial Sloan-Kettering Cancer Center, 1250 First Avenue, 10021, New York, New York

    Neal Flomenberg M.D. & Bo Dupont

  2. Department of Pathology, College of Physicians and Surgeons, Columbia University, 168th Street and Broadway, 10036, New York, New York

    Carlo Russo & Soldano Ferrone

Authors
  1. Neal Flomenberg M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlo Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Soldano Ferrone
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bo Dupont
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Flomenberg, N., Russo, C., Ferrone, S. et al. HLA class l specific t lymphocyte clones with dual alloreactive functions. Immunogenetics 19, 39–51 (1984). https://doi.org/10.1007/BF00364474

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00364474

Keywords

Search

Navigation