Molecular linkage of the mouse CD5 and CD6 genes

• Published in: Immunogenetics (New York) 1996, Vol.44 (5), p.385-390
• Main Authors: Lecomte, O, Bock, J B, Birren, B W, Vollrath, D, Parnes, J R
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - genetics; Antigens, Differentiation, T-Lymphocyte - genetics; Base Sequence; CD5 Antigens - genetics; Chromosome Mapping; Genes; Genetic Linkage; Mice - genetics; Molecular Sequence Data; Multigene Family
• ISSN: 0093-7711
• DOI: 10.1007/BF02602784

CD5 and CD6 are both lymphocyte cell surface glycoproteins that appear to play a role in T-cell activation. In humans, CD6 is a 105 000 /130 000 M sub(r) monomer expressed at high levels by peripheral blood T cells and medullary thymocytes, and also by a small fraction of peripheral blood B cells. The mouse homologue has recently been shown to be a 130 000 M sub(r) glycoprotein expressed on the surface of thymocytes and T cells in lymph node and spleen. Monoclonal antibody (mAb) crosslinking studies have shown that CD6 ligation in combination with costimulatory signals provided by accessory cells, PMA or anti-CD2/CD3 mAbs can induce proliferation of human T cells. CD5 is a 67 000 M sub(r) monomeric glycoprotein expressed on all mature T cells, most thymocytes, and a subset of mature B cells. Like CD6, CD5 also seems to play an important role in T-cell activation both in humans and mice, as crosslinking of CD5 by mAbs enhances T-cell proliferation either in a monocyte-dependent manner or in response to mitogens, alloantigens, or CD3-specific mAbs. Furthermore, CD5 is physically associated with the Tcr/CD3 complex on T cells. In addition to their similar tissue distribution and costimulatory activity in T cells, CD5 and CD6 are also structurally related molecules: they both belong to the scavenger receptor cysteine rich (SRCR) protein superfamily defined by the cysteine-rich domain of the type I macrophage scavenger receptor. This domain includes a 100 amino acid stretch with six positionally conserved cysteine residues. CD5 and CD6 are particularly close homologues, since they are so far the only members of this family possessing three SRCR domains, and they additionally share two cysteine residues and 31 conserved residues in their SRCR domains that are not found in other members of the SRCR family. Furthermore, the human CD5 and CD6 genes have both been mapped to chromosome 11. In mouse, the CD5 gene has been mapped to chromosome 19. Because the CD5 and CD6 genes are related and map to the same chromosome in human, the present study was undertaken to look for a possible linkage between the mouse CD5 and CD6 genes. To address this question, we performed pulse field gel electrophoresis (PFGE) experiments using DNA from the mouse CD4 super(+) T-cell line C6VL (obtained from J. Allison, University of Berkeley, CA), which expresses both CD5 and CD6.