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Southern blot analysis using a genomic probe of the human TCR-gamma chain first variable gene subgroup (V gamma I) was performed on DNA samples from both parents of 36 healthy Caucasian families. Two types of polymorphisms were found in these 72 unrelated DNA samples: three repertoire polymorphisms and two restriction fragment length polymorphisms (RFLP). In all cases, Mendelian inheritance of these polymorphisms was demonstrated. The most frequent repertoire polymorphism consists in the lack of the V gamma 4 and V gamma 5 segments. In 16% of chromosomes, the Eco RI and Taq I restriction fragments corresponding to V gamma 4 and V gamma 5 were lacking, with no additional bands. In these cases, a decrease of 10 kb was observed in the Bam HI fragment containing all V gamma I segments as compared with samples containing V gamma 4-V gamma 5 segments. To better understand this polymorphism, which takes place in a previously incompletely defined region, the central part of the V gamma I region, including the polymorphic V gamma 4-V gamma 5 segments, was cloned. This allowed us to localize precisely the V gamma 5 segment and thus complete the description of the V gamma I region. A striking homology of DNA and deduced amino acid sequences is present between V gamma 2 and V gamma 4 and between V gamma 3 and V gamma 5, much higher than that observed between V gamma 2 and V gamma 3 and between V gamma 4 and V gamma 5. The differences in nucleotide sequence occur mainly in the intron and three hypervariable regions. These results strongly suggest a gene duplication relationship between the segments V gamma 2-V gamma 3 and the segments V gamma 4-V gamma 5. The most frequent RFLP documented in this study is due to the combined absence of the Eco RI and the Taq I sites located in the noncoding region between V gamma 3 and V gamma 4. The haplotypic frequence of this RFLP is 6.9% of the general population. As the gamma/delta receptor may play an important role in immunological response, the biological relevance of the high degree of polymorphism occurring in the V gamma I region, as well as its possible association with some immune disturbances, should be further explored.

The V gamma locus of the human T cell receptor gamma gene. Repertoire polymorphism of the first variable gene segment subgroup.