What was known before?
Histocompatibility antigens had for a long time been known as extraordinarily strong
antigens and responsible for graft rejection, but their physiological function was obscure.
At the time, recent experiments in mice had indicated that cooperation between T and B
cells or T cells and macrophages only occurred in H-2 compatible systems. Another new
aspect was a recently observed correlation between MHC phenotype and susceptibility to
lymphocytic choriomeningitis virus. The technique of chromium release assays had just been
established. Zinkernagel and Doherty decided to apply this technique to investigate the
role of histocompatibility antigens in virus-specific immune responses.
The important questions
Is the magnitude of murine virus-specific T cell response correlated with the H-2 type?
Will comparison of cytotoxicity in different MHC haplotypes shed light on the virtual
function of MHC molecules?
The experiment
Related papers
Zinkernagel RM, Doherty PC. 1974. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic
system.
Nature 248: 701-2

Zinkernagel RM, Doherty PC. 1974. Immunological surveillance against altered self components by sensitised T lymphocytes in lymphocytic
choriomeningitis.
Nature 251: 547-8