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October 4, 1995, Vol 274, No. 13 >
ARTICLE | October 4, 1995

MHC-Restricted T-cell Recognition: Title and subTitle BreakThe Basis of Immune Surveillance FREE

Rolf M. Zinkernagel, MD
[+] Author Affiliations

Dr Zinkernagel is the recipient of the 1995 Albert Lasker Basic Medical Research Award.

Reprint requests to Institute of Experimental Immunology, University Hospital of Zurich, Schmelzbergstr 12, CH-8091 Zurich, Switzerland (Dr Zinkernagel).


JAMA. 1995;274(13):1069-1071. doi:10.1001/jama.1995.03530130075034
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References

IN 1973, immunology was preoccupied with graft rejection and immune responses against model antigens. The biological function of transplantation antigens coded by the major histocompatibility gene complex (MHC) was unknown; clearly its function was not to render organ transplantation difficult. This changed when MHC restriction of T-cell recognition was discovered by two young immunologists. The historical background to this effort is discussed in the accompanying article by Peter Doherty.1 This article describes the experiments that were done at that time, summarizes subsequent advances that led to our current understanding of how T cells work, and discusses some of the consequences for clinical medicine.

EXPERIMENTAL CHANCE AND DISCOVERY  After an internship in Basel and studies in Lausanne with H. Isliber, I obtained a Swiss fellowship to work with R. V. Blanden and Peter Doherty in G. Ada's department in Canberra. Peter Doherty and I joined forces to analyze the nature

REFERENCES

1 +
Doherty PC.  The keys to cell-mediated immunity. JAMA . 1995;;274:1067-1068.
2 +
Doherty PC, Zinkernagel RM.  T cell-mediated immunopathology in viral infections. Transplant Rev . 1974;;19:89-120.
3 +
Oldstone MBA, Dixon FJ, Mitchell GF, McDevitt HO.  Histocompatibility-linked genetic control of disease susceptibility. J Exp Med . 1973;;137:1201-1211.
4 +
Zinkernagel RM, Doherty PC.  Restriction of in vitro T cell mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature . 1974;;248:701-702.
5 +
Zinkernagel RM, Doherty PC.  Immunological surveillance against altered self components by sensitized T lymphocytes in lymphocytic choriomeningitis. Nature . 1974;;251:547-548.
6 +
Shearer GM.  Cell-mediated cytotoxicity to trinitrophenyl-modified syneneic lymphocytes. Eur J Immunol . 1974;;4:527-533.
7 +
Rosenthal AS, Shevach EM.  Function of macrophages in antigen recognition by guinea pig T lymphocytes, I: requirement for histocompatible macrophages and lymphocytes. J Exp Med . 1973;; 138:1194-1212.
8 +
Katz DH, Hamaoka T, Benacerraf B.  Cell interactions between histoincompatible T and B lymphocytes, II: failure of physiologic cooperative interactions between T and B lymphocytes from allogeneic donor strains in humoral response to hapten-protein conjugates. J Exp Med . 1973;;137:1405-1418.
9 +
Klein J.  The major histocompatibility complex of the mouse. Science . 1979;;203:516-522.
10 +
McMichael AJ, Ting A, Zweerink HJ, Askonas BA.  HLA restriction of cell-mediated lysis of influenza virus-infected human cells. Nature . 1977;; 270:524-526.
11 +
Goulmy E, Termijtelen A, Bradley BA, VanRood JJ.  Y-antigen killing by T cells of woman is restricted by HLA. Nature . 1977;;266:544-545.
12 +
Zinkernagel RM, Callahan GN, Althage A, Cooper S, Klein PA, Klein J.  On the thymus in the differentiation of 'H-2 self-recognition' by T cells. J Exp Med . 1978;;147:882-896.
13 +
Fink PJ, Bevan MJ.  H-2 antigens of the thymus determine lymphocyte specificity. J Exp Med . 1978;; 148:766-775.
14 +
Miller JFAP.  Immunological function of the thymus. Lancet . 1961;;2:748-749.
15 +
Townsend ARM, Rothbard J, Gotch FM, Bahadur G, Wraith D, McMichael AJ.  The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell . 1986;;44:959-968.
16 +
Doherty PC, Zinkernagel RM.  A biological role for the major histocompatibility antigens. Lancet . 1975;;2:1406-1409.
17 +
Dausset J, Svejgaard A. HLA and Disease . Copenhagen, Denmark: Munksgaard; 1977;:9.
18 +
Zinkernagel RM.  Associations between major histocompatibility antigens and susceptibility to disease. Annu Rev Microbiol . 1979;;33:201-213.
19 +
Zinkernagel RM, Pircher HP, Ohashi PS, et al.  T and B cell tolerance and responses to viral antigens in transgenic mice. Immunol Rev . 1991;;122: 133-171.

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1 +
Doherty PC.  The keys to cell-mediated immunity. JAMA . 1995;;274:1067-1068.
2 +
Doherty PC, Zinkernagel RM.  T cell-mediated immunopathology in viral infections. Transplant Rev . 1974;;19:89-120.
3 +
Oldstone MBA, Dixon FJ, Mitchell GF, McDevitt HO.  Histocompatibility-linked genetic control of disease susceptibility. J Exp Med . 1973;;137:1201-1211.
4 +
Zinkernagel RM, Doherty PC.  Restriction of in vitro T cell mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature . 1974;;248:701-702.
5 +
Zinkernagel RM, Doherty PC.  Immunological surveillance against altered self components by sensitized T lymphocytes in lymphocytic choriomeningitis. Nature . 1974;;251:547-548.
6 +
Shearer GM.  Cell-mediated cytotoxicity to trinitrophenyl-modified syneneic lymphocytes. Eur J Immunol . 1974;;4:527-533.
7 +
Rosenthal AS, Shevach EM.  Function of macrophages in antigen recognition by guinea pig T lymphocytes, I: requirement for histocompatible macrophages and lymphocytes. J Exp Med . 1973;; 138:1194-1212.
8 +
Katz DH, Hamaoka T, Benacerraf B.  Cell interactions between histoincompatible T and B lymphocytes, II: failure of physiologic cooperative interactions between T and B lymphocytes from allogeneic donor strains in humoral response to hapten-protein conjugates. J Exp Med . 1973;;137:1405-1418.
9 +
Klein J.  The major histocompatibility complex of the mouse. Science . 1979;;203:516-522.
10 +
McMichael AJ, Ting A, Zweerink HJ, Askonas BA.  HLA restriction of cell-mediated lysis of influenza virus-infected human cells. Nature . 1977;; 270:524-526.
11 +
Goulmy E, Termijtelen A, Bradley BA, VanRood JJ.  Y-antigen killing by T cells of woman is restricted by HLA. Nature . 1977;;266:544-545.
12 +
Zinkernagel RM, Callahan GN, Althage A, Cooper S, Klein PA, Klein J.  On the thymus in the differentiation of 'H-2 self-recognition' by T cells. J Exp Med . 1978;;147:882-896.
13 +
Fink PJ, Bevan MJ.  H-2 antigens of the thymus determine lymphocyte specificity. J Exp Med . 1978;; 148:766-775.
14 +
Miller JFAP.  Immunological function of the thymus. Lancet . 1961;;2:748-749.
15 +
Townsend ARM, Rothbard J, Gotch FM, Bahadur G, Wraith D, McMichael AJ.  The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell . 1986;;44:959-968.
16 +
Doherty PC, Zinkernagel RM.  A biological role for the major histocompatibility antigens. Lancet . 1975;;2:1406-1409.
17 +
Dausset J, Svejgaard A. HLA and Disease . Copenhagen, Denmark: Munksgaard; 1977;:9.
18 +
Zinkernagel RM.  Associations between major histocompatibility antigens and susceptibility to disease. Annu Rev Microbiol . 1979;;33:201-213.
19 +
Zinkernagel RM, Pircher HP, Ohashi PS, et al.  T and B cell tolerance and responses to viral antigens in transgenic mice. Immunol Rev . 1991;;122: 133-171.

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