Skip to main content
SpringerLink
Log in

Characterization of human T-lymphocyte clones (TLCs) specific for HLA-region gene products

  • Original Investigations
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

Clones of lymphocytes, primed in vitro to HLA-DR1; Dw1, were tested for allospecific proliferation on a panel of thirty-one HLA-phenotyped stimulating cells. No clone was restimulated exclusively by cells sharing the DR1; Dw1 priming antigens and most clones were restimulated by subsets of cells bearing DR1; Dw1. Generally, positive responses were at least 20-fold higher than autologous negative controls. Peak proliferative responses occurred around 72 h and varied, depending on the stimulating cell as well as the responding clone. Selected clones were induced to proliferate only by cells incapable of forming rosettes with sheep erythrocytes. Specific proliferation by TLCs was blocked by monoclonal DR-specific antibodies, but not by monoclonal anti-Thy 1.2. Genetic studies demonstrated that TLCs detected some cell-surface determinants that are encoded by genes in linkage disequilibrium with HLA and others that may not be linked to the human 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

3HTdR:

tritiated methylthymidine

HTC:

homozygous typing cell

MHC:

major histocompatibility complex

HLA:

human MHC

MLC:

mixed leukocyte culture

PBL:

peripheral blood lymphocytes

PLT:

primed lymphocyte typing

TCGF:

T-cell growth factor

IL-2:

interleukin 2

TLC:

T-lymphocyte close

References

  • Amos, D. B. and Kostyu, D. D.: HLA- A central immunological agency of man. In H. Harris and K. Hirschorn (eds.): Adv. Hum. Genet. 10: 137–208, 1980

  • Bach, F. H. and Hirschorn, K.: Lymphocyte interaction: A potential histocompatibility test in vitro. Science 143: 813–814, 1964

    Google Scholar 

  • Bach, F. H., Inouye, H., Hank, J. A., and Alter, B. J.: Human T lymphocyte clones reactive in primed lymphocyte typing and cytotoxicity. Nature 281: 307–309, 1979

    Google Scholar 

  • Bain, B., Vas, M. R., and Lowenstein, L.: The development of large mononuclear cells in mixed leukocyte cultures. Blood 23: 108–116, 1964

    Google Scholar 

  • Charmer, D., Mawas, C., Kristensen, T., and Mercier, P.: The HLA-D system: At least two loci and four distinct phenotypic traits per haplotype. Introduction to component typing in families and population by primed lymphocyte typing. Immunogenetics 13: 57–84, 1981

    Google Scholar 

  • Dorf, M. E.: Complementation of H-2-Linked genes controlling immune responsiveness. Springer Sem. Immunopathol. 1: 171–206, 1978

    Google Scholar 

  • Duquesnoy, R. J., Marrari, M., and Ammen, K.: Association of the B-cell alloantigen MB1 with HLA-DRwl and DRw2. Transplant. Proc. 12: 138–140, 1980

    Google Scholar 

  • Eckels, D. D. and Hartzman, R. J.: Evidence for a T-lymphocyte clone (TLC) restimulating determinant encoded by a new gene linked to HLA. Hum. Immunol. 3: 337–343, 1981

    Google Scholar 

  • Eckels, D. D., Woody, J. N., and Hartzman, R. J.: Monoclonal and xenoantibodies specific for HLA-DR inhibit primary responses to HLA-D but fail to inhibit secondary proliferative (PLT) responses to allogeneic cells. Hum. Immunol. 3: 133–142, 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: 57–79, 1981

    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, 1979

    Google Scholar 

  • Goulmy, E., Blokland, E., van Rood, J., Charmot, D., Malissen, B., and Mawas, C.: Production, expansion and clonal analysis of T cells with specific HLA-restricted male lysis. J. Exp. Med. 152: 182s-190s, 1980.

    Google Scholar 

  • Hartzman, R. J., Pappas, F., Romano, P. J., Johnson, A. H., Ward, F. E., and Amos, D. B.: Dissociation of HLA-D and HLA-DR using primed LD typing. Transplant. Proc. 10: 809–812, 1978

    Google Scholar 

  • Inouye, H., Hank, J. A., Alter, B. J., and Bach, F. H.: TCGF production for cloning and growth of functional human T lymphocytes. Scand. J. Immunol. 12: 149–154, 1980

    Google Scholar 

  • Johnson, A. H., Ward, F. E. and Amos, D. B.: B lymphocyte alloantigens. Scand. J. Immunol. 6: 403–408, 1977

    Google Scholar 

  • Joysey, V. C. and Wolf, E.: HLA-A, -B and -C antigens, their serology and cross-reaction. Br. Med. Bull. 34: 217–222, 1978

    Google Scholar 

  • 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 virusimmune clone. J. Immunol. 128: 233–238, 1982

    Google Scholar 

  • Markert, M. L. and Cresswell, P.: Polymorphism of human B-cell alloantigens: Evidence for three loci within the HLA system. Proc. Natl. Acad. Sci. U.S.A. 77: 6101–6104, 1980

    Google Scholar 

  • Mawas, C., Charmot, D., and Mercier, P.: Split of HLA-D into two regions alpha and beta by a recombination between HLA-D and GLO. I. Study in a family and primed lymphocyte typing for determinants coded by the beta region. Tissue Antigens 15: 458–466, 1980

    Google Scholar 

  • Mendell, N. R., Lee, K. L., Reinsmoen, N., Yunis, E., Amos, D. B., and Emme, L.: Statistical methods for evaluating responses in HLA-D typing. Transplant. Proc. 9: 99–106, 1977

    Google Scholar 

  • Morgan, D. A., Ruscetti, F. W., and Gallo, R.: Selective in vitro growth of T lymphocytes from normal human bone marrows. Science 193: 1007–1008, 1976

    Google Scholar 

  • Morling, N., Jakobsen, B. K., Platz, P., Ryder, L. P., Svejgaard, A., and Thompsen, M.: Correlations between HLA-D/DR associated primed lymphocyte typing (PLT) defined DP-antigens, HLA-D and HLA-DR antigens. Tissue Antigens 17: 421–427, 1981

    Google Scholar 

  • Pawelec, G. and Wernet, P.: Restimulation of human Allorgactive cloned T-cell lines. Dissection of HLA-D-region alleles in population studies and in family segregation analysis. Immunogenetics 11: 507–519, 1980

    Google Scholar 

  • Reinsmoen, N. L., Noreen, H. J., Sasazuki, T., Segall, M., and Bach, F. H.: Roles of HLA-D antigens in haplotype-primed LD typing reagents. In J. Gordin Kaplan (ed.): The Molecular Basis of Immune Cell Function, pp. 529–537, Elsevier/North Holland Biomedical Press, Amsterdam, 1979

    Google Scholar 

  • Ruscetti, F. W., Morgan, D. A., and Gallo, R. C.: Functional and morphologic characterization of human T cells continuously grown in vitro. J. Immunol. 199: 131–138, 1977

    Google Scholar 

  • Sachs, J. A., Joraquemada, D., and Festenstein, H.: Intra-HLA-D region recombinant maps HLA-DR between HLA-B and HLA-D. Tissue Antigens 17: 43–56, 1981

    Google Scholar 

  • Shackelford, D. A., Strominger, J. L., Mann, D. L., and van Rood, J. J.: Biochemical characterization of the human B cell alloantigen DC1(MT1, LB12) and comparison to the HLA-DR antigen. Proc. Natl. Acad. Sci. U.S.A. 78: 4566–4570, 1981

    Google Scholar 

  • Shaw, S., Johnson, A. H. and Shearer, G. M.: Evidence for a new segregant series of B cell antigens that are encoded in the HLA-D region and that stimulate secondary allogeneic proliferative and cytotoxic responses. J. Exp. Med. 152: 565–580, 1980a

    Google Scholar 

  • Shaw, S., Pollack, M. S., Payne, S. M., and Johnson, A. H.: HLA-linked B cell alloantigens of a new segregant series: Population and family studies of the SB antigen. Hum. Immunol. 1: 177–185, 1980b

    Google Scholar 

  • Sheehy, M. J., Sondel, P. M., Bach, M. L., Wank, R., and Bach, F. H.: HL-A LD (lymphocyte defined) typing: A rapid assay with primed lymphocytes. Science 188: 1308–1310, 1975

    Google Scholar 

  • Suciu, A. and Suciu-Foca, N.: The genetics of LD2. 1. Gene frequency: An estimation. Transplant. Proc. 11: 1323–1326, 1979

    Google Scholar 

  • Suciu-Foca, N. and Dausset, J.: Complex MLR family patterns. Immunogenetics 2: 389–391, 1975

    Google Scholar 

  • Suciu-Foca, N., Godfrey, M., Rohowsky, C., McKiernan, P., Susinno, E., and Broell, J.: Evidence that HLA-D is different from DR and that two different HLA loci code for B-cell antigens. Transplant. Proc. 11: 1732–1734, 1979

    Google Scholar 

  • Suciu-Foca, N., Godfrey, M., Suciu, A., Kahn, R., Rohowsky, C., Malavet, J., Sawczick, A., Woodward, K., Susinno, E., and Hardy, M.: Checkerbeards between 8WHTCs: Polymorphism of LD2 or heterogeneity of HLA-D antigens? In P.I. Terasaki (ed.): Histocompatibility Testing 1980, pp. 883–885, UCLA Tissue Typing Laboratory, 1980

  • Tanigaki, N., Tosi, R., Pressman, D., and Ferrara, G. B.: Molecular identification of human la antigens coded for by a gene locus closely linked to HLA-DR locus. Immunogenetics 10: 151–167, 1980

    Google Scholar 

  • Termijtelen, A., Bradley, B. A., and vanRood, J. J.: A new determinant, defined by PLT, coded for in the HLA region and apparently independent of the HLA-D and DR loci. Tissue Antigens 15: 267–274, 1980

    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. Transplant. Proc. 9: 1771, 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 

Download references

Author information

Authors and Affiliations

  1. Division of Immunologic Oncology, Vincent T. Lombardi Cancer Research Center, and the Departments of Pediatrics and Microbiology, Georgetown University School of Medicine, Washington D. C.

    David D. Eckelsl

  2. Transplantation and Immunology Branch, Naval Medical Research Institute, Bethesda, Maryland

    Robert J. Hartzman

Authors
  1. David D. Eckelsl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert J. Hartzman
    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

Eckelsl, D.D., Hartzman, R.J. Characterization of human T-lymphocyte clones (TLCs) specific for HLA-region gene products. Immunogenetics 16, 117–133 (1982). https://doi.org/10.1007/BF00364399

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00364399

Keywords

Search

Navigation