Liu Z, Harris P E, Colovai A I, Reed E F, Maffei A, Suciu-Foca N
College of Physicians and Surgeons of Columbia University, Department of Pathology, New York, New York 10032, USA.
Clin Immunol Immunopathol. 1996 Mar;78(3):228-35. doi: 10.1006/clin.1996.0034.
To investigate the role of the indirect pathway of recognition in human allograft rejection, we have mapped the dominant T cell determinant of the HLA-DRbeta10101 molecule presented by the DRbeta11101 antigen. A synthetic peptide (pp 22-35) corresponding to the sequence of the dominant peptide determinant was used for testing the frequency of in vivo activated T cells in the graft and in the periphery. DRbeta1*1101-positive patients carrying a heart allograft mismatched for the HLA-DR1 antigen showed no reactivity to pp 22-35 during quiescence. However, interleukin-2-responsive T cells, which were pp 22-35 specific, were found in the circulation prior to and at the time of acute and chronic rejection. The response of in vivo and in vitro activated T cells was inhibited at high concentrations of peptide 22-35. This data suggests that indirect recognition plays an important role in allograft rejection and that it can be abolished by high zone tolerance induction.
为研究间接识别途径在人类同种异体移植排斥反应中的作用，我们绘制了由DRbeta11101抗原呈递的HLA-DRbeta10101分子的主要T细胞决定簇图谱。使用与主要肽决定簇序列相对应的合成肽（第22 - 35位氨基酸）来检测移植物和外周血中体内活化T细胞的频率。携带与HLA-DR1抗原不匹配的心脏同种异体移植物的DRbeta1*1101阳性患者在静止期对第22 - 35位氨基酸合成肽无反应。然而，在急性和慢性排斥反应之前及反应期间，在循环中发现了对第22 - 35位氨基酸合成肽特异的白细胞介素-2反应性T细胞。在高浓度的第22 - 35位氨基酸合成肽存在时，体内和体外活化T细胞的反应均受到抑制。该数据表明间接识别在同种异体移植排斥反应中起重要作用，并且高区耐受性诱导可消除这种作用。
