Breiteneder H, Scheiner O, Hajek R, Hulla W, Hüttinger R, Fischer G, Kraft D, Ebner C
Institute of General and Experimental Pathology, University of Vienna, Austria.
Immunogenetics. 1995;42(1):53-8. doi: 10.1007/BF00164987.
T-cell clones (TCC) were raised from the peripheral blood of patients suffering from tree pollen allergy. All TCC were restricted by HLA-DR molecules. In order to investigate possible intervention targets in Type I allergic diseases, we examined T-cell receptor (TCR) alpha and beta chain nucleotide sequences of five allergen-reactive human CD4+ TCC specific for a C-terminal epitope (BV 144) of Bet v 1, the major birch pollen allergen. Proliferation assays using synthetic peptides revealed the 10-mer LRAVESYLLA as minimal epitope for three TCC; two TCC also displayed reactivity with the nonapeptide LRAVESYLL. Two TCC expressed TCRBV2S3, all other BV144-specific TCC used diverse TCRAV and TCRBV gene segments. Moreover, the junctional regions encoding the third complementary determining regions (CDR3) of the TCR showed a striking heterogeneity in length and amino acid composition. Nevertheless, all TCC showed an arginine residue in the N-terminal region of their TCRBV CDR3 loops. Therefore, therapeutical strategies aimed at the clonal deletion of allergen-specific T-cell clones, providing help for IgE synthesis, will not be feasible. Our results cast a doubt on the theory that the CDR3 exclusively provides the primary contact with the peptide bound in the major histocompatibility (MHC) groove, and suggest additional interaction with MHC class II.
从患有树花粉过敏症患者的外周血中培养出T细胞克隆（TCC）。所有TCC均受HLA - DR分子限制。为了研究I型过敏性疾病中可能的干预靶点，我们检测了五个针对主要桦树花粉过敏原Bet v 1的C末端表位（BV 144）的过敏原反应性人CD4 + TCC的T细胞受体（TCR）α和β链核苷酸序列。使用合成肽进行的增殖试验表明，10聚体LRAVESYLLA是三个TCC的最小表位；两个TCC也与九聚体LRAVESYLL有反应。两个TCC表达TCRBV2S3，所有其他BV144特异性TCC使用不同的TCRAV和TCRBV基因片段。此外，编码TCR第三互补决定区（CDR3）的连接区在长度和氨基酸组成上显示出显著的异质性。然而，所有TCC在其TCRBV CDR3环的N末端区域都有一个精氨酸残基。因此，旨在克隆清除为IgE合成提供帮助的过敏原特异性T细胞克隆的治疗策略将不可行。我们的结果对CDR3专门提供与主要组织相容性（MHC）凹槽中结合肽的主要接触的理论提出了质疑，并表明与II类MHC存在额外的相互作用。
