Peter Doherty, Nobel Laureate: Questions and Reflections Concerning MHC Restriction and other Fruits of a Life of Biomedical Erudition

Neil S. Greenspan


In 1974, Peter Doherty and Rolf Zinkernagel published a landmark article in Nature [1] that described the ability of lymphocytic choriomeningitis virus (LCMV)-specific cytotoxic T cells to lyse LCMV-infected, 51Cr-labeled target cells if the target cells shared class I major histocompatibility complex (MHC) molecules with these T cells. Surprisingly, infected and labeled target cells with disparate class I MHC molecules were not lysed. This phenomenon, which came to be known as “MHC restriction,” was a major advance in our understanding of the way in which T cells recognize antigen and was ultimately the basis for the awarding of the 1996 Nobel Prize in Physiology or Medicine to Peter Doherty and Rolf Zinkernagel. Readers interested in more information on Dr. Doherty or on MHC restriction are referred to the relevant pages of the Nobel Prize website [2].


T-cell recognition; Viral immunology; Vaccines; The nature of scientific progress

Full Text:



1. Zinkernagel RM, Doherty PC. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature. 1974;248(5450):701-2. PubMed PMID: 4133807.

2. Doherty PC. Peter C. Doherty - Biographical Nobel Media 1996 [accessed on 11/26/18]. Available from: https://

3. Zinkernagel RM, Doherty PC. The discovery of MHC restriction. Immunol Today. 1997;18(1):14-7. PubMed PMID: 9018968.

4. Kuhn TS. The Structure of Scientific Revolutions. 2nd ed. Chicago and London: University of Chicago Press; 1962.

5. Kindred B, Shreffler DC. H-2 dependence of co-operation between T and B cells in vivo. J Immunol. 1972;109(5):940-3. PubMed PMID: 4538719.

6. Katz DH, Hamaoka T, Dorf ME, Benacerraf B. Cell interactions between histoincompatible T and B lymphocytes. The H-2 gene complex determines successful physiologic lymphocyte interactions. Proc Natl Acad Sci U S A. 1973;70(9):2624-8. PubMed PMID: 4126264. Pubmed Central PMCID: 427069.

7. 1995 Lasker Awards: Albert And Mary Lasker Foundation; [accessed on 11/26/18]. Available from:

8. Bevan MJ. The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens. J Exp Med. 1975;142(6):1349-64. PubMed PMID: 53263. Pubmed Central PMCID: 2190072.

9. Schmitt-Verhulst AM, Shearer GM. Bifunctional major histocompatibility-linked genetic regulation of cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes. J Exp Med. 1975;142(4):914-27. PubMed PMID: 52685. Pubmed Central PMCID: 2189948.

10. 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(5):1194-212. PubMed PMID: 4542806. Pubmed Central PMCID: 2139433.

11. 1995 LASKER AWARDS: 1995 Albert Lasker Basic Medical Research Award: Albert And Mary Lasker Foundation; [Accessed on 11/26/18]. Available from:


  • There are currently no refbacks.

Copyright (c) 2018 Neil S. Greenspan

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

© Pathogens and Immunity 2019

Case Western Reserve University; Division of Infectious Diseases

10900 Euclid Ave.; Mailstop 4984; Cleveland, OH 44106

(216) 368-6317; ISSN: 2469-2964;