Vγ (I) Expression in Human Intestinal Lymphocytes is Restricted

Abstract

The majority of human intestinal intraepithelial lymphocytes (HIELS) express CD8+, and the T cell Receptor (TCR) αβ. A minority of HIELS utilize TCR γ δ chains. Vo is established as the TCR-δ expressed by most TCRγ δ HIELS. Since Vδ1 is the dominant intestinal TCR and γ (I) family is preferentially used in forming a heterodimer, this study was conducted to characterize individual Vγ (I) utilization in HIELS. Intestinal lymphocytes were isolated from four samples of colonic epithelium obtained from patients undergoing colon resection or endoscopy. RNA was isolated and cDNA synthesized. PCR amplification was performed with consensus Jγ and Vγ primers in these regions. PCR products were cloned and sequenced. All samples had Vγ4 transcripts, a majority Vγ3 whereas Vγ2 and Vγ8 were less frequent. No Vγ2 transcripts had any predicted TCR protein products. Similarly, very few potentially productive Vγ3 transcripts were found. In contrast, almost all Vγ4 transcripts were found to be in-frame and the only Vγ8 transcript was in-frame. The CDR3 region of the γ transcripts were small compared to published intestinal TCR δ recombinations. All CDR3 regions contained at least one charged amino acid. The limited number of functional transcripts adds evidence to the oligoclonality of intestinal TCRs expressing the TCR Vγ (I) family. The short CDR3 regions support the concept of limited antigen recognition by this lymphocyte population.