Summary The murine CD48 molecule is a member of the immunoglobulin superfamily which regulates the activa- tion of T lymphocytes. Prior cloning experiments using mRNA from two different mouse strains had yielded discrepant sequences within the IgV-like domain of murine CD48. To resolve this issue, we have directly sequenced genomic DNA of 10 laboratory strains and two inbred strains of wild origin. The results of our analysis reveal an allelic polymorphism within the IgV- like domain of murine CD48. The CD48 (Blast-1, BCM1, sgp-60) antigen is a cell surface molecule involved in the activation of murine T lymphocytes. Expression of CD48 is tightly con- trolled and restricted to lymphocytes, macrophages and dendritic cells; the molecule becomes upregulated upon cell activation. The counter-receptor of CD48 is CD2 (T11) (Kato et al., 1992), the expression of which is similar to that of CD48 (Davis & van der Merwe, 1996). Antibodies to either CD2 or CD48 can block T-cell activation in vitro (Arvieux et al., 1986; Reiser, 1990; Kato et al., 1992; Sen et al., 1992) and immune responses in vivo (Qin et al., 1994). Moreover, recent studies indicate that T cells from CD48-deficient mice are defective in activation (our unpublished data). CD48 is a member of the immunoglobulin (Ig) superfamily and, based on sequence homology and common chromosomal location, belongs to a subfam- ily of the Ig superfamily that – among other proteins – also includes its counter-receptor CD2 (Davis & van der Merwe, 1996). The cDNA for murine CD48 has been isolated and is predicted to encode a protein com- posed of a signal peptide followed by an IgV-like domain, an IgC-like domain, and a membrane-anchor- ing domain (Wong et al., 1990; Cabrero et al., 1993). Several findings have raised the possibility of an allelic polymorphism within the IgV-like domain of murine CD48. Experiments in which CD48 was purified from a C57BL/6-derived T-cell line and subjected to microsequencing revealed the presence of an asparagine at residue 68 (Cabrero et al., 1993). The same amino acid was predicted from cDNA cloning experiments (codon AAT; nucleotides 318–320) in which lymphocyte mRNA from C57BL/6 mice was used as starting material for the construction of the library (Wong et al., 1990). In contrast, when CD48 was cloned from a BALB/c library the codon GAT was identified at the same position, predicting the presence of aspartic acid at residue 68 (Cabrero et al., 1993). Taken together these findings suggested the presence of an allelic polymorphism in the V-like domain of murine CD48. To further investigate this point we have directly sequenced genomic DNA from a total of 12 inbred strains. Of these strains, 10 were laboratory strains and two were inbred strains derived from wild origin. The results of the sequencing experiments are summarized in Fig. 1a. These data confirm that the Cd48 locus is characterized by an allelic polymorphism. Of the 10 laboratory strains examined, only C57BL/6J mice (accession number AF064620) carry codon AAT at position 318–320, whereas all other strains, including A/J (accession number AF064615), AKR/J (accession number AF064616), BALB/cJ (accession number AF064617), CBA/J (accession number AF064618), C3H/HeJ (accession number AF064619), DBA/1J (accession number AF064621), DBA/2J (accession number AF064622), SJL/J (accession number AF064623) and 129/SvJ (accession number AF064624) carry the codon GAT at this position. These data are consistent with prior cDNA and peptide sequence anal- ysis and indicate that the CD48 protein derived from C57BL/6J mice carries an asparagine at amino acid residue 68 whereas the other laboratory strains carry aspartate at this position (Fig. 1b). Based on the results of molecular modelling studies by van der Merwe et al. (van der Merwe et al., 1995), this polymorphism is unlikely to affect binding of CD48 to its counter-recep- tor CD2; whether it has other functional consequences remains to be determined. Today’s classical laboratory strains represent a © 1998 Blackwell Science Ltd, European Journal of Immunogenetics 25, 421–423 The murine Cd48 gene: allelic polymorphism in the IgV-like region J. G. Cabrero,* G. J. Freeman† & H. Reiser‡ 421 * Unidad de Investigacíon, Fundación Jiménez Díaz, Madrid, Spain, †Department of Medicine, Harvard Medical School, Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, USA, and ‡Department of Immunology, Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London, UK Received 10 July 1998; accepted 20 August 1998 Correspondence: Professor Hans Reiser, Department of Immunology, Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK Short Communication