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Human Ig superfamily CTLA‐4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA‐4 cytoplasmic domains

The mouse CTLA‐4 gene has been shown to code for an activated lymphocyte‐associated sequence belonging to the Ig gene superfamily. We now report on the molecular cloning and study of the human corresponding gene isolated from a genomic library and designated Hu‐CTLA‐4. The Hu‐CTLA‐4 gene exists as a single copy per human haploid genome and maps to band q33 of chromosome 2. It comprises 3 exons notwithstanding the leader sequence. The first exon encodes a V‐like domain of 116 amino acids, the second one a hydrophobic putative transmembrane region of 37 amino acids and the third one a 34 amino acid putative cytoplasmic domain. Whereas the overall homology between the human and murine CTLA‐4 proteins is 76%, there is, remarkably, a complete identity of their cytoplasmic domains. This complete interspecies conservation comes in support of an important role for this domain in CTLA‐4 function.