CD1 : une nouvelle famille de molécules présentatrices d'antigènes aux caractéristiques singulières.

Abstract

Decouvertes il y a une vingtaine d' annees, les glycoproteines membranaires CD1 partagent, avec les produits classiques des genes du CMH, une similitude de structure et un role de presentation des antigenes a des lymphocytes T. La nature singuliere des antigenes presentes par les molecules CD1 et le mecanisme cellulaire conduisant a leur presentation font du systeme restreint par les molecules CD1 un systeme particulier, complementaire du systeme conventionnel sous le controle du CMH. Parallelement aux lymphocytes T CD1 restreints, il existe une population de lymphocytes T CD1 autoreactifs. Parmi ces derniers, certaines sous-populations conservees entre l' homme et la souris pourraient regler la reponse immunitaire contre les agents pathogenes, avoir une fonction antitumorale et controler certains phenomenes d' auto-immunite. Certaines de ces cellules autoreactives sont capables de reconnaitre des antigenes glycolipidiques et pourraient reconnaitre des glycolipides du soi presentes par CD1. Ce phenomene, qui semble dote d' une certaine specificite tissulaire, pourrait jouer un role dans le controle de l' homeostasie tissulaire.

CD1 molecules are related to major histocompatibility complex-encoded antigen presenting molecules in both structure and evolution, however they exhibit relatively little polymorphism. The human CD1 family consists of four known proteins. CD1a, CD1b and CD1c proteins are closely related and expressed predominantly on specialized antigen presenting cells in a wide variety of tissues. A unique role for these three molecules is their ability to mediate the specific T-cell recognition of various lipids and glycolipids derived from the cell wall of pathogenic mycobacteria including Mycobacterium tuberculosis and Mycobacterium l1prae. Investigation of human leprosy has provided direct evidence suggesting that the CD1-mediated pathway of antigen recognition plays a significant role in protective immune response to microbial pathogens in vivo. A fourth human CDI protein, CD1d is involved in activation of invariant Valpha24JalphaQ TCR+ T cells. Data obtained from patients with systemic scleroderma and type 1 diabetes suggest that this subset of T cells may be functionally related to resistance or progression of autoimmune disease in humans. Counterparts for Valpha24JalphaQ TCR+ human T cells were previously described in mouse. The mouse T cells express the semi-invariant Valpha14Jalpha281 TCR, the lectin NK1.1 and react to mouse CD1d. These so-called NK1.1+ T cells are capable of early secretory burst 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 for IL-12 dependent rejection of tumors and involved in the immune response to pathogens. Like Valpha24JalphaQ TCR+ cells in human, NK1.1+ cells are quantitatively and functionally deficient in several autoimmune-prone mice. NK1.1+ T cells may be able to distinguish between a diverse set of CD1d-bound self-ligands. Recently cellular glycosylphoshatidylinositol was found to be a natural ligand of CD1d and glycosylceramides were shown to activate NK1.1+ T cells in a CD1d restricted fashion. Given these recently accumulated datas, it is likely that the CD1 system of antigen presenting contributes greatly to several immune-based defense and homeostatic. [References: 40]