Skip to main content

Advertisement

Log in

Mixed lymphocyte reactions for individuals with phenotypic identity for specific HLA-B, DR determinants: The role of linkage disequilibrium and of specific DR and other class II determinants

  • Original Articles
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Although many patients who might benefit from therapeutic bone marrow transplantation lack HLA identical sibling donors, results from many centers now indicate that transplants involving donors other than identical siblings have been successful in a substantial number of cases. Most of these cases were selected because cells from the patient and donor were compatible in mixed lymphocyte culture. We have previously shown that the prediction of mixed lymphocyte culture nonreactivity by HLA-B,DR matching is far more successful if the matched donors shared antigen combinations known to possess significant positive linkage disequilibrium. We now also show that cells from donors with unrelated haplotypes having the specific DR determinants DR1, DR2, and DR3 are more likely than cells from donors with other haplotypes to be mutually compatible in mixed lymphocyte culture. However, even cells from donors with haplotypes with the highest levels of positive linkage disequilibrium frequently show significant mutual stimulation which can, in selected family studies, be attributed to determinants like SB that map between HLA-D/DR and GLO.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Clift RA, Hansen JA, Thomas ED, Buckner CD, Sanders JE, Mickelson EM, Storb R, Johnson FL, Singer JW, Goodell BW: Marrow transplantation from donors other than HLA-identical siblings. Transplantation 28:235–242, 1979

    Google Scholar 

  2. Hansen JA, Clift RA, Mickelson EM, Nisperos B, Thomas ED: Marrow transplantation from donors other than HLA identical siblings. Hum Immunol 2:31–40, 1980

    Google Scholar 

  3. Dupont B, O'Reilly RJ, Pollack MS, Good RA: Use of HLA genotypically different donors in bone marrow transplantation. Transplant Proc 11:219–224, 1979

    Google Scholar 

  4. Dupont B, O'Reilly RJ, Pollack MS, Good RA: Histocompatibility testing for clinical bone marrow transplantation and prospects for identification of donors other than HLA genotypically identical siblings.In Immunobiology of Bone Marrow Transplantation, S Thierfelder, H Rodt, HJ Kolb (eds). Berlin, Springer, 1980, pp 121–134

    Google Scholar 

  5. Dupont B: HLA factors and bone marrow graftingIn Cancer, Achievements, Challenges and Prospects for the 1980's, Vol. 2, JH Burchenal, HF Oettgen (eds). New York, Grune & Stratton, 1981, pp 683–693

    Google Scholar 

  6. Goldmann SF: Selection of related and unrelated bone marrow donors. Transplant Proc 9:507–511, 1977

    Google Scholar 

  7. Vaidya S, Colbaugh P, Stastny P: Predictive value of HLA-DR matching for non-reactivity in mixed lymphocyte culture (MLC) depends on matching for HLA-D. Transplant Proc 11:1779–1780, 1979

    Google Scholar 

  8. Pollack MS, Chin-Louie J, Callaway C, Blanco M, Sullivan K, O'Reilly RJ, Dupont B: Selection of unrelated bone marrow transplantation donors for patients with HLA-B/DR haplotypes with significant genetic disequilibrium. Transplant Proc (in press), 1983

  9. Baur MP, Danilovs JA: Reference tables of two and three-locus haplotype frequencies for HLA-A,B,C,DR,BF, and GLO.In Histocompatibility Testing 1980, PI Terasaki (ed). Los Angeles, UCLA Tissue Typing Laboratory, 1980, pp 994–1210

    Google Scholar 

  10. Danilovs J, Terasaki PI, Park MS, Ayoub G: B lymphocyte isolation by thrombin-nylon wool.In Histocompatibility Testing 1890, PI Terasaki (ed). Los Angeles, UCLA Tissue Typing Laboratory, 1980, pp 287–288

    Google Scholar 

  11. Kömpf J, Biddbort S, Gussman S, rittner H: Polymorphism of red cell gloxylase I (E.C. 4.4. 1.5.). A new genetic marker in man. Humangenetik 27:141, 1975

    Google Scholar 

  12. Hansen JA, Good RA, Dupont B: HLA-D compatibility between parent and child: Increased occurrence in severe combined immunodeficiency and other hematopoietic diseases. Transplantation 23:366–374, 1977

    Google Scholar 

  13. Dupont B: Immunogenetic Aspects of the Human Mixed Lymphocyte Culture Reaction. Meilgaard, Denmark, GMT, 1978 (dissertation)

    Google Scholar 

  14. Baur MP, Danilovs JA: Population analysis of HLA-A,B,C,DR and other genetic markers.In Histocompatibility Testing 1980, PI Terasaki (ed). Los Angeles, UCLA Tissue Typing Laboratory, 1980, pp 955–993

    Google Scholar 

  15. Zar J: Biostatistical Analysis. Englewood Cliffs, NJ, Prentice Hall, 1974, pp 114–115, 236–241, 246–248

    Google Scholar 

  16. Shaw S, Kavathas P, Pollack MS, Charmot D, Mawas C: Family studies define a new histocompatibility locus SB, between HLA-DR and GLO. Nature 293:745, 1981

    Google Scholar 

  17. Shaw S, DeMars R, Schlossman SF, Smith PL, Lampson LA, Nadler LM: Serologic identification of the human secondary B cell antigens. Correlation between function, genetics, and structure. J Exp Med 156:731–743, 1982

    Google Scholar 

  18. Pawelec G, Shaw S, Schneider M, Blaurock M, Frauer M, Brackertz D, Wernet P: Population studies of HLA-linked SB antigens and their relative importance in primary MLC typing. Analysis of HLA-D homozygous typing cells and normal heterozygous populations. Hum Immunol 5:215–223, 1982

    Google Scholar 

  19. O'Reilly RJ, Kapoor N, Kirkpatrick D: Fetal tissue transplants for severe combined immunodeficiency—their limitations and functional potential.In Primary Immunodeficiencies, M Seligmann, W Hitzig II (ed). Amsterdam, Elsevier/North Holland, 1980, pp 419–433

    Google Scholar 

  20. Martin PJ, Torok-Storb B, Hansen JA, Thomas ED: Preclinical evaluation of murine monoclonal antibodies for selective depletion of T cells in donor marrow in human marrow transplantation.In Abstracts Annual Meeting, American Association for Clinical Histocompatibility Testing, 1982, p A21

  21. Reisner Y, Kapoor N, Kirkpatrick D, Pollack MS, Dupont B, Chaganti RSK, Good RA, O'Reilly RJ: Transplantation for acute leukemia using HLA-A,B,C non-identical parental marrow cells fractionated with soybean agglutinun and sheep red blood cells. Lancet 2:327–331, 1981

    Google Scholar 

  22. O'Reilly RJ, Dupont B, Pahwa S, Grimes E, Smithwick EM, Pahwa R, Schwartz S, Hansen JA, Siegal FP, Sorell M, Svejgaard A, Jersild C, Thomsen M, Platz P, L'Esperance P, Good RA: Reconstitution in severe combined immunodeficiency by transplantation of marrow from an unrelated donor. N Engl J Med 297:1311–1318, 1977

    Google Scholar 

  23. Jeannet M, Speck B, Sartorius J: Donor selection for bone marrow transplantation: Predictive value of DR typing for mixed lymphocyte culture compatibility between unrelated individuals. Transplantation 26:448–449, 1978

    Google Scholar 

  24. O'Reilly RJ, Pahwa R, Kirkpatrick D, Sorell M, Kapadia A, Kapoor N, Hansen JA, Pollack MS, Schutzer SE, Good RA, Dupont B: Successful transplantation of marrow from an HLA:A,B,D mismatched heterozygous sibling donor into an HLA-D homozygous patient with aplastic anemia. Transplant Proc 10:957–962, 1978

    Google Scholar 

  25. Hansen JA, Clift RA, Thomas ED, Buckner CD, Storb R, Giblett ER: Transplantation of marrow from an unrelated donor to a patient with acute leukemia. N Engl J Med 303:565–567, 1980

    Google Scholar 

  26. Duquesnoy R, Marrari M, Hackbarth S, Zeevi A, Camitta B: Bone marrow transplantation of a patient with aplastic anemia from an HLA identical unrelated donor. Hum Immunol 5:146, 1982

    Google Scholar 

  27. Dupont B, Hansen JA: Donor selection for bone marrow transplantation: The predictive value of HLA-D typing for MLR compatibility between unrelated individuals. Transplant Proc 10:53–56, 1978

    Google Scholar 

  28. van Rood JJ, van Leeuwen A, Goulmy E, Termijtelen A, Bradley BA, Brand A, Eernisse: The importance of non-HLA systems and the feasibility of the use of unrelated donors in bone marrow transplantation. Transplant Proc 10:47–52, 1978

    Google Scholar 

  29. Bodmer WF, Bodmer JG: Evolution and function of the HLA system. Br Med Bull 34:309–316, 1978

    Google Scholar 

  30. Alper CA, Awdeh ZL, Raum DD, Yunis EJ: Extended major histocompatibility complex haplotypes in man: Role of alleles analogous to murine t mutants. Clin Immunol Immunopathol 24:276–285, 1978

    Google Scholar 

  31. Awdeh Z, Raum D, Yunis EJ, Alper CA: Complotype-HLA linkage: Evidence for extended haplotypes and human t-like mutants.In Abstracts, Fourth International Workshop for the Genetics of Complement, Boston, 1982, p 4

  32. Dupont B, Braun DW, Yunis EJ, Carpenter CB: HLA-D by cellular typing.In Histocompatibility Testing 1980, PI Terasaki (ed). Los Angeles, UCLA, 1980, pp 229–267

    Google Scholar 

  33. Reinsmoen NL, Bach FL: Five HLA-D cluster associated with HLA-DR4. Hum Immunol 4:249–258, 1982

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pollack, M.S., Chin-Louie, J., Callaway, C. et al. Mixed lymphocyte reactions for individuals with phenotypic identity for specific HLA-B, DR determinants: The role of linkage disequilibrium and of specific DR and other class II determinants. J Clin Immunol 3, 341–351 (1983). https://doi.org/10.1007/BF00915795

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00915795

Key words

Navigation