GENOMIC ORGANIZATION OF THE MOUSE T-CELL RECEPTOR V-ALPHA FAMILY

Based on the analysis of Vα gene segment deletions in a panel of T lymphomas, we have constructed a map of the mouse T cell receptor α/δ region and assigned the relative position of 72 distinct V gene segments. Three major observations have emerged from such studies. First, members of a given Vα subfamily are not organized in discrete units along the chromosome but largely interspersed with members of other Vα subfamilies. Second, analysis of the deletion map suggests the existence of repetitive patterns (Vα clusters) in the chromosomal distribution of the Vα gene segments. Third, the present-day organization of the Vα/δ region may be readily explained by a series of sequential duplications involving three ancestral Vα clusters. Direct evidence for the existence of these unique structural features has been gained by cloning ~ 370 kb of DNA and positioning 26 distinct Vα gene segments belonging to six different subfamilies. Finally, the relationships existing between the Vα/δ gene segment organization and usage are discussed in terms of position-dependent models.