MHC CLASS-I MOLECULE-RESTRICTED PRESENTATION OF VIRAL-ANTIGEN IN BETA(2)-MICROGLOBULIN-DEFICIENT MICE

Normally, Ag is presented to CD8(+) T lymphocytes as a tripartite complex consisting of peptide epitope, MHC-encoded class I heavy (alpha) chain, and beta(2)-microglobulin (beta(2)-m) light chain. Although there is agreement about the function of both peptide and alpha-chain, the role of beta(2)-m has remained uncertain. In particular, can Ag be presented without its participation? We have sought to obtain an answer by using mice in which the gene for beta(2)-m had been disrupted by homologous recombination. As a consequence, no light chains are synthesized and, furthermore, few if any CD8(+) T lymphocytes are formed. Elimination of lymphocytic choriomeningitis (LCM) virus from the tissues of acutely infected mice is mediated solely by CD8(+) T lymphocytes; hence, in the beta(2)-m-lacking mutants the infection cannot be terminated. Here it is shown that infusion of immune spleen cells from syngeneic B-2-m(+)/(+) mice and from mice compatible in K or D of the MHC resulted in virus clearance. Approximately five times more cells were required to achieve antiviral effects in beta(2)-m-deficient than in wild-type mice but attempts to improve elimination by treatment of the former with IFN-gamma or beta(2)-m have failed. Depleting the immune splenocytes of CD8(+) T lymphocytes but not of CD4(+) T lymphocytes abolished the antiviral potential. We conclude that LCM virus-infected murine cells can present viral Ag to CD8(+) effector T lymphocytes together with class I MHC molecules K and D, despite the total absence of beta(2)-m.