MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULES AND RESISTANCE AGAINST INTRACELLULAR PATHOGENS

The immune system employs a temporal hierarchy of effector mechanisms to combat infections by intracellular pathogens. The nonspecific respo nse is independent of MHC and can be activated rapidly, while the spec ific response is slower, more specific, and requires major histocompat ibility complex (MHC) molecules. MHC-dependent responses have been cha racterized extensively in vitro for antigens presented by polymorphic MHC class Ia and class II proteins and recognized by T lymphocytes car rying alpha/beta T-cell receptors (TcR). Growing indirect evidence has implicated monomorphic MHC class Ib proteins and gamma/delta T lympho cytes in defense against bacterial infections, but the biochemical and immunological behavior of class Ib proteins and gamma/delta TcR has n ot been well characterized, and most hypotheses involving these protei ns have relied on data obtained with polymorphic MHC proteins and alph a/beta TcR. An overview of studies describing bacterial infections in vivo suggests that, in many cases, MHC class I-dependent effector cell s may not be indispensable for effective immune responses, exerting in stead a modulatory effect during the course of infection. Furthermore, many class Ib proteins have probably specialized to present stress an tigens and conserved microbial antigens, which may be recognized by ga mma/delta T cells through an interaction that is qualitatively very di fferent from alpha/beta TcR binding to class I and class II proteins.