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 response is independent of MHC and can be activated rapidly, while the specific response is slower, more specific, and requires major histocompatibility complex (MHC) molecules. MHC-dependent responses have been characterized extensively in vitro for antigens presented by polymorphic MHC class Ia and class II proteins and recognized by T lymphocytes carrying α/β T-cell receptors (TcR). Growing indirect evidence has implicated monomorphic MHC class Ib proteins and γ/δ T lymphocytes in defense against bacterial infections, but the biochemical and immunological behavior of class Ib proteins and γ/δ TcR has not been well characterized, and most hypotheses involving these proteins have relied on data obtained with polymorphic MHC proteins and α/β TcR. An overview of studies describing bacterial infections in vivo suggests that, in many cases, MHC class I-dependent effector cells may not be indispensable for effective immune responses, exerting instead a modulatory effect during the course of infection. Furthermore, many class Ib proteins have probably specialized to present stress antigens and conserved microbial antigens, which may be recognized by γ/δ T cells through an interaction that is qualitatively very different from α/β TcR binding to class I and class III proteins.