Two distinct T-cell receptor α-chain transcripts in a rabbit T-cell line: Implications for allelic exclusion in T cells

Abstract

Information relevant to allelic exclusion in T cells has been obtained by a study of cDNA clones corresponding to α-chain genes of the T-cell receptor in the rabbit T-cell line RL-5. One clone contains a variable-joining-constant (VJC) sequence encoding a complete α chain of the T-cell receptor. A second has an identical constant region and includes a distinct variable-joining (VJ) sequence. However, a single-base deletion in the variable region places the remainder of the second transcript out-of-phase and appears to be the product of a rearrangement involving a variable region of the T-cell receptor α-chain pseudogene. Presence of two variable-joining-constant (VJC) transcripts in the same cell line indicates that α-chain gene rearrangement is not affected by transcription of a complete α-chain mRNA and suggests that steps after mRNA synthesis are involved in the allelic exclusion process for α-chain genes. Comparision of rabbit α-chain sequences with those of man and mouse revealed interspecies conservation in constant and variable regions. Genomic Southern blot analyses using a rabbit constant region of the T-cell receptor α-chain probe revealed the presence of a single constant region gene. Hybridization with variable region probes defined two distinct multigenic subfamilies. Homology between certain rabbit and murine variable regions of the T-cell receptor α-chain sequences suggests that the existence of subfamilies predated divergence of these species.