DeCloux A, Woods A S, Cotter R J, Soloski M J, Forman J
Department of Medicine, Johns Hopkins University Medical School, Baltimore, MD 21205, USA.
J Immunol. 1997 Mar 1;158(5):2183-91.
One of the hallmarks of class I(A) molecules is their ability to bind and present a wide array of peptides to CD8 T cells. This diversity is consistent with their ability to restrict a variety of pathogenic peptide epitopes as well as elicit strong transplantation responses. In contrast, class I(B) molecules appear to be involved in presentation of pathogenic epitopes to a relatively lesser extent as well as play a minor role in transplantation responses. Here we have examined the peptides bound and presented by the class I(B) molecule Qa-1b in order to determine if their diversity was similar to that reported for class I(A) Ags. First, we show that bulk-cultured anti-Qa-1b CTL predominantly recognize a single peptide (Qdm) derived from the leader segment of class I(A) alloantigens. These CTL are peptide specific and reflect the activity of previously described CTL clones. Second, we find approximately 4.6 x 10(4) copies of the Qdm peptide/cell. Most of the peptide is Qa-1b associated since the recovery of this peptide from anti-Qa-1b immunoprecipitates is approximately 75% of that seen in whole cell extracts and no detectable activity is observed in Kb or Db extracts from H-2b lymphoblasts. Third, the expression of Qa-1b on lymphoblasts is approximately 1 to 1.25 x 10(4) molecules/cell indicating that the Qdm peptide must be derived from both cell membrane and intracellular compartments. Finally, examination of the diversity of peptides associated with Qa-1b as determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry indicates few detectable peptide species associated with this molecule. Taken together, Qa-1b appears to predominantly bind a single peptide species that is recognized by alloreactive CD8 T cells. This feature may account, in part, for the class I(B) properties of this molecule.
I类（A）分子的一个标志是它们能够结合并向CD8 T细胞呈递多种肽段。这种多样性与其限制多种致病肽表位以及引发强烈移植反应的能力相一致。相比之下，I类（B）分子似乎在致病表位的呈递中参与程度相对较低，并且在移植反应中起次要作用。在这里，我们研究了与I类（B）分子Qa-1b结合并呈递的肽段，以确定它们的多样性是否与I类（A）抗原报道的相似。首先，我们表明大量培养的抗Qa-1b CTL主要识别一种源自I类（A）同种异体抗原前导序列的单一肽段（Qdm）。这些CTL具有肽特异性，反映了先前描述的CTL克隆的活性。其次，我们发现每个细胞约有4.6×10⁴个Qdm肽段拷贝。大多数肽段与Qa-1b相关，因为从抗Qa-1b免疫沉淀中回收的该肽段约为全细胞提取物中所见的75%，并且在H-2b淋巴母细胞的Kb或Db提取物中未观察到可检测到的活性。第三，淋巴母细胞上Qa-1b的表达约为1至1.25×10⁴个分子/细胞，这表明Qdm肽段必定源自细胞膜和细胞内区室。最后，通过基质辅助激光解吸/电离飞行时间质谱法确定与Qa-1b相关的肽段多样性，结果表明与该分子相关的可检测肽种类很少。综上所述，Qa-1b似乎主要结合一种被同种反应性CD8 T细胞识别的单一肽种类。这一特征可能部分解释了该分子的I类（B）特性。
