T CELL RECEPTOR ??-CHAIN REPERTOIRES ARE NONRANDOMLY SELECTED IN RESPONSES TO HLA-DR11

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Abstract
T cell receptor (TCR) β-chain usage by HLA-DR1 alloreactive T cell lines was examined to determine whether common TCR gene segments were used preferentially. We have demonstrated previously that a DR1-specific, human renal allograft-derived T cell line and replicate anti-DR1 mixed lymphocyte reactions (MLR), established from an unrelated responder/stimulator pair, were selected for T cells expressing Vβ8. In this report, the Vβ8+ β-chains from these T cell lines were sequenced to assess clonality and determine the contribution made by the β-chain junctional regions. All 11 Vβ8+ cDNA clones sequenced from the allograft-derived T cell line used Jβ2.7 and Cβ2 and had identical junctions, indicating the presence of a predominant Vβ8+ clone. All seven Vβ8+ sequences from the first anti-DR1 MLR and eight of nine from the second also used Jβ2.7 and Cβ2 and were identical to one another, indicating that a common Vβ8+ clone was selected in these replicate cultures. The sequences of the predominant Vβ8+ β-chains from the allograft-derived T cell line and the MLR differed by only 10 nucleotides and four amino acids at the VDJβ junction. To determine the reproducibility of TCR Vβ selection in responses to DR1, additional MLR were established by pairing three different DR1+ stimulators with the same responder. The TCR repertoires of the resulting DR1-specific cell lines were examined. A preference was seen for utilization of certain homologous TCR Vβ segments. The data suggest that particular TCR Vβ or Vβ/Jβ combinations may be selected in alloresponses as evidenced either by utilization of highly similar β-chains or homologous Vβ segments.