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We asked Jack Strominger, a long-time collaborator and friend of Don Wiley's, to share with us the excitement of working out the structures of the major histocompatibility antigens.
For over 75 years, only humoral antibodies were known to mediate immunological specificity. The apparent absence of these in delayed-type hypersensitivity reactions was perplexing, and the dominant dogma of antibodies led to some curious hypotheses.
T cells bearing two different TCRs can be detrimental because the unselected TCR has the potential to cause autoimmunity. Evidence is now emerging that the unselected TCR may also be beneficial by expanding the TCR repertoire for foreign antigens.
Autoreactive T cells may escape tolerance induction owing to enzymatic cleavage of dominant determinants in the thymus. Processing events both in the thymus and the periphery influence the spectrum of determinants available to T cells.
Functionally active inhibitory receptors that impart negative signals have been found recently on T cells. One such inhibitory receptor, CD94-NKG2A, can induce cytolytic anergy in CTLs specific for polyomavirus.
Immunoglobulins secreted by memory B cells dominate secondary humoral responses. New evidence suggests the cytoplasmic tails of BCRs confer an advantage to cells expressing IgG, leading to their sustained proliferation and immunoglobulin production
Leukocyte arrest on inflamed endothelium constitutes only the first phase of their recruitment into the tissues. New data points to the roles played by JAM-1 and CD99 in leukocyte passage through the barrier posed by the vascular endothelium during inflammatory responses.
In response to microbial infections, Drosophila mounts a multifaceted immune response involving humoral reactions that culminate in the destruction of invading organisms by lytic peptides. These defense mechanisms are activated via two distinct signaling pathways. One of these, the Toll pathway, controls resistance to fungal and Gram-positive bacterial infections, whereas the Imd pathway is responsible for defense against Gram-negative bacterial infections. Current evidence indicates that recognition of infectious nonself agents results from interactions between microbial wall components and extracellular pattern recognition proteins. We discuss here evolutionary perspectives on our present understanding of the antimicrobial defenses of Drosophila.
