Recognition of antigenic peptide and MHC molecule by T cell receptor

• Main Authors: Shen, Yu-Chi, 沈玉琪
• Other Authors: Lai, Ming-Zong
• Format: Others
• Language: zh-TW
• Published: 1994
• Online Access: http://ndltd.ncl.edu.tw/handle/75677203366558607526

碩士 === 國立陽明大學 === 微生物暨免疫學研究所 === 82 === T淋巴球以其細胞受體(TCR)，辨識已和抗原呈獻細胞表面主要組織相容性複合體形成複合體之外來胜月太。儘管主要組織相容性複合體和胜月太間交互作用已被研究得很透徹它們如何分別被T細胞受體辨認仍不清楚。本研究以了被I-Ek及I-Ad所呈獻的抗原胜月太λrepressor cI 12-26作為模式，分別從三方面探討T細胞受體和胜月太-主要組織相容性複合體的作用情形。 在T細胞受體如何辨識I-Ek呈獻的cI 12-26方面係利用cl 12-26在I-Ek結合位置剛被定出，而藉改變cI 12-26其他位置對細胞活性之影響以確認與每一個T細胞受體之接觸位置。T細胞對I-Ek呈獻的cI 12-26的辨識是非常限定的，在十株獨立細胞中有九株辨認Arg17,Lys19,Tyr22,及Lys24。另一株51V細胞只和cI 16-26的N端部分(Arg16,Arg17,Lys19)有交互作用。T細胞受體辨識點之分析明顯地指出在兩對相鄰相同的可能接觸位置中(Arg16,17;Lys24,25)，只有一個(Arg17,Lys24)優先被T細胞受體辨認。 在了解T細胞受體辨認cI 12-26時如何與I-Ek接觸方面我們利用在α螺旋區域有各種不同突變的I-Ek來呈獻cI12-26給T細他以決定其最重要接觸點。結果顯示所有T細胞(包括51V)是和I-Ek β鏈α螺旋的中間部分接觸，而α鏈在對T細胞受體的接觸上較不重要。這也指出T細胞與I-Ek之接觸並不決定於T細胞受體與cI 12-26之接觸。 在T細胞對I-Ad呈獻的cI 12-26的辨識方面，實驗結果顯示和I-Ek呈獻時不同，且其辨識是多樣性的。有些細胞只辨認Arg17,Lysl9，及Tyr22，另一些細胞還和cI 12-26的N端部分進行作和第三群細胞則額外和Glu23,Lys24接觸，第四群細胞額外和Lys24接觸。目前的研究結果幫助我們了解T細胞受體胜月太和主要組織相容性複合體之間確實的分子交互作用關係。 T lymphocytes recognize antigenic peptides bound to MHC molecules on the surfaces of antigen presenting cells. This recognition is mediated by the αβ T cell receptor (TCR). The interaction between MHC and peptides has been well characterized. How TCR interacts with antigenic peptide and MHC molecule are largely unknown. We use I-Ek and I-Ad restricted λ represser cI 12-26 as a model system, to elucidate the interaction between TCR and antigen-MHC complex. The I-Ek anchoring residues of cI 12-26 has recently been located. The exact contact sites on cI 12-26 was then determined by the T cell inactivity to cl 12-26 with site-specific mutation on each of non-anchoring residue. T cell recognition of I-Ek-presented cI 12-26 is highly restricted, in which 9 out of 10 independent T cells recognize Argl7, Lysl9, Tyr22 and Lys24. The other T cell 51V interacts only with the N-terminal part of cI 16-26 (Argl6, Argl7, Lysl9), suggesting an additional way of generating T cell diversity. Notably, in the two adjacent potential TCR-contacting residues (Argl6,17; Lys24,25), only one (Argl7, Lys24) will be preferentially recognized. To understand how TCR interacts with I-Ek during the recognition of cl 12-26, I-Ek with mutations at a helical regions were used to present cl 12-26 to different T cells. The results indicate that all T cells (including 51V) are in contact with the central part of α-helix of the I-Ek β chain. The a. chain of I-Ek is less important for contacting with TCR. These results indicate that contact of T cell and I-Ek is not determined by the interaction of TCR and cI 12-26. On the recognition of I-Ad-presented cI 12-26 by TCR, the TCR- contacting residues of cI 12-26 are different from that presented by I-Ek In addition, T cell reactivity toward cl 12-26 presented by I-Ad is highly diverse. Some T cells recognize only Argl7, Lysl9 and Tyr22. The others interact additionally with the N-terminal residues of cI 12-26. A third group of TCR is also in contact with Glu23 and Lys24, and the fourth group recognizes Glu23 in addition. The present study helps understanding the exact molecular interaction between TCR, antigen and MHC, and provides basis for modulation of such interaction.