The Role of MHC Gene Products in Immune Regulation and its Relevance to Alloreactivity

The immune system has evolved the eapacity to react specifically with a very large number of foreign molecules with which it had no previous contact, while avoiding reactivity for aulotogous molecules, naturally antigenic in other species or in other individuals ofthe same species. Immunological research has been directed to the elucidation of this phenomenon ever since Ehrlich [I] proposed that immunocompetent cells bear receptors for antigen idenlical wilh lhe antibodies to be produced. Gowans [2] identified lymphocytes as the eells responsible for immune phenomena. Burnet [3] proposed theelonal selection theory of immunity which postulated that (1) lymphocytes differentiate as clones bearing antibody receptors oi unique specificity, and (2) antibody responses reflect the selective expansion of specific lymphocytes, following lhe binding ofaiitigen, and their differentiation as seeretors ofantibody, idenlieal in specificity with the antigen binding reeeptors on the original clones. The Burnet hypothesis was verified experimentally [4-6] and was aeeepted as a major advance, concerned primarily with the response of antibody producing cells, later identified as B lymphoeytes [7] and plasma eells. Accordingly, studies on the specificity of antibodies and on the structure of immunoglobulins revealed that Ihese molecules [8. 9] and their structural genes [10. 11] evolved in a way that ensures the enormous diversity of antibody combining sites observed.