CD1, a new and noteworthy lineage of antigen presenting molecules

CD1 molecules are related to major histocompatibility complex-encoded antig en presenting molecules in both structure and evolution, however they exhib it relatively little polymorphism. The human CD1 family consists of four kn own proteins. CD1a, CD1b and CD1c proteins are closely related and expresse d predominantly on specialized antigen presenting cells in a wide variety o f tissues. A unique role for these three molecules is their ability to medi ate the specific T-cell recognition of various lipids and glycolipids deriv ed from the cell wall of pathogenic mycobacteria including Mycobacterium tu berculosis and Mycobacterium leprae. Investigation of human leprosy has pro vided direct evidence suggesting that the CD1-mediated pathway of antigen r ecognition plays a significant role in protective immune response to microb ial pathogens in vivo. A fourth human CD1 protein, CD1d is involved in acti vation of invariant V alpha 24J alpha Q TCR+ T cells. Data obtained from pa tients with systemic scleroderma and type 1 diabetes suggest that this subs et of T cells may be functionally related to resistance or progression of a utoimmune disease in humans. Counterparts for V alpha 24J alpha q TCR+ huma n T cells were previously described in mouse. the mouse T cells express the semi-invariant V alpha 24J alpha 281 TCR, the lectin NK1.1 and react to mo use CD1d. These so-called NK1.1(+) T cells are capable of early secretory b urst of IL-4 and IFN-gamma which are believed to promote T cell bias toward TH1 or Th2 effector cell differentiation. NK1.1(+) T cells are required fo r IL-12 dependent rejection of tumors and involved in the immune response t o pathogens. Like V alpha 24J alpha Q TCR+ cells in human, NK1.1(+) cells a re quantitatively and functionally deficient in several autoimmune-prone mi ce. NK1.1(+) T cells may be able to distinguish between a diverse set of CD 1d- bound self-ligands. Recently cellular glycosylphoshatidylinositol was f ound to be a natural ligand of CD1d and glycosylceramides were shown to act ivate NK1.1(+) T cells in a CD1d restricted fashion. Given these recently a ccumulated dates, it is likely that the CD1 system of antigen presenting co ntributes greatly to several immune-based defense and homeostatic systems.