CD1 molecules are a relatively new member of MHC family, which came to light during a search for non-classical MHC I molecules such as the TL molecules of mice. In contrast to TL, however, CD1 genes are not linked to the MHC. They associate with b2 microglobulin, but their expression is independent of TAP. There are 5 CD1 genes in humans, named a-e and 2 in mice, named 1.1 and 1.2. The al and a2 domains of CD1 are quite different from MHC I, hence they cannot be modelled on the basis of MHCI. In the humans, CD1 is divided into groups, the first group contains CD1 a-c, while d, which is the most distant from them is in a group by itself. a-c are expressed primarily in antigen presenting cells, and some lymphocytes while d is more ubiquitous. The known mouse CD1 molecules fall into the second category. Very little is known about the antigen presenting function of CD1:two human CD1s of the first group have been shown to present lipids, while one mouse CD1 (of the second group) has been shown to present a peptide. T cells also appear to react to CD1 molecules without any ligand specificity. In mice, there is some evidence that the NK1.1+ T cells are CD1-reactive. CD1 molecules appear to combine the features of MHCI and MHC II. The main MHC I like features are association with b2 microglobulin (although this is not universally so), binding to CD8 ( although binding to CD4 is also recorded) and the requirement of highly-restricted anchor positions in the ligands, whose mutations at these sites abrogates binding. The MHC II like features are : preference for longer peptides, TAP-independence of presentation and chloroquine - sensitivity of presentation of some ligands. This table of characteristics is derived from a rather sketchy information on a small number of examples. Given the above, the investigator aims to : define the means by which the antigens to be presented by CD1 are taken up by APCs, track the antigen inside the APCs, track CD1 inside the APC, determine the site of interaction of CD1 with antigen and identify other molecules which associate with CD1.
| Lawton, Anna P; Prigozy, Theodore I; Brossay, Laurent et al. (2005) The mouse CD1d cytoplasmic tail mediates CD1d trafficking and antigen presentation by adaptor protein 3-dependent and -independent mechanisms. J Immunol 174:3179-86 |
| Sullivan, Barbara A; Nagarajan, Niranjana A; Kronenberg, Mitchell (2005) CD1 and MHC II find different means to the same end. Trends Immunol 26:282-8 |
| Dougan, Stephanie K; Salas, Azucena; Rava, Paul et al. (2005) Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells. J Exp Med 202:529-39 |
| Elewaut, Dirk; Lawton, Anna P; Nagarajan, Niranjana A et al. (2003) The adaptor protein AP-3 is required for CD1d-mediated antigen presentation of glycosphingolipids and development of Valpha14i NKT cells. J Exp Med 198:1133-46 |
| Brossay, L; Tangri, S; Bix, M et al. (1998) Mouse CD1-autoreactive T cells have diverse patterns of reactivity to CD1+ targets. J Immunol 160:3681-8 |
