Yassine-Diab B, Carmichael P, L'Faqihi F E, Lombardi G, Deacock S, de Préval C, Coppin H, Lechler R I
U.395 INSERM, IFR 30 INSERM-UPS-CNRS-CHU, CHU Purpan, Toulouse, France.
Immunogenetics. 1999 Jun;49(6):532-40. doi: 10.1007/s002510050531.
A comprehensive analysis was carried out of the tri-molecular complex of peptide, major histocompatibility class II molecule, and T-cell receptor (TcR) involved in the recognition of the promiscuous HA (306-318) peptide, restricted by one of two closely related HLA-DR alleles, HLA-DRB10101 and HLA-DRB10103. These two DR molecules differ by only three amino acids at positions 67, 70, and 71, in the third variable region of the DRB1 chain. None of the HA (306-318)-specific T-cell clones restricted by these two DR molecules tolerated amino acid substitution at the peptide-binding position 71, despite the fact that the substitution did not interfere with peptide binding. The majority of the DRB10103-restricted clones tolerated substitution of the amino acid at the TcR-contacting position 70, while the DRB10101-restricted T cells did not. Based usage of TRVA and TRVB segments was observed for the DRB10103-restricted clones; in contrast, apparently random usage was seen in the DRB10101-restricted T cells. Finally, limiting dilution analysis revealed a lower frequency of T cells reactive with the HA peptide in a DRB10103 compared with a DRB10101 individual. Taken together these data suggest that biased TcR gene usage may reflect a relatively low precursor frequency of T cells, and the need for clonal expansion of a limited set of high avidity T cells.
对涉及识别混杂性HA（306 - 318）肽的肽、主要组织相容性复合体II类分子和T细胞受体（TcR）的三分子复合物进行了全面分析，该识别受两个密切相关的HLA - DR等位基因之一HLA - DRB10101和HLA - DRB10103的限制。这两种DR分子在DRB1链的第三个可变区中，仅在第67、70和71位氨基酸上存在三个氨基酸的差异。尽管肽结合位置71处的氨基酸取代并不干扰肽结合，但受这两种DR分子限制的HA（306 - 318）特异性T细胞克隆均不能耐受该位置的氨基酸取代。大多数受DRB10103限制的克隆能够耐受TcR接触位置70处的氨基酸取代，而受DRB10101限制的T细胞则不能。对于受DRB10103限制的克隆，观察到TRVA和TRVB片段的使用存在偏向性；相反，在受DRB10101限制的T细胞中，使用情况明显随机。最后，有限稀释分析显示，与携带DRB10101的个体相比，携带DRB10103的个体中与HA肽反应的T细胞频率较低。综合这些数据表明，TcR基因使用的偏向性可能反映了T细胞相对较低的前体频率，以及有限数量的高亲和力T细胞进行克隆扩增的必要性。
