Berzofsky J A, Brett S J, Streicher H Z, Takahashi H
Metabolism Branch, National Cancer Institute, Bethesda, Maryland 20892.
Immunol Rev. 1988 Dec;106:5-31. doi: 10.1111/j.1600-065x.1988.tb00771.x.
Antigen processing encompasses the metabolic events that a protein antigen must undergo in or on the antigen-presenting cell before it can be recognized by the T lymphocyte. It appears that a primary goal of these events is to unfold the protein to expose residues that are buried in the native conformation, which is designed to be soluble in water. The APC usually accomplishes this task by proteolytic cleavage of the protein, but we have found that artificial unfolding without proteolysis is sufficient. The purpose of unfolding may be to allow different faces of the antigenic site to bind simultaneously to the T-cell receptor and the MHC molecule on the APC, or to interact with other structures on the membrane of the APC. This requirement for unfolding appears to apply to everything from small peptides to large multimeric proteins. We have found that the way the antigen is processed and the structure of the fragments produced can greatly affect the availability of antigenic sites. For instance, some antigenic sites are not recognized when the native protein is used as immunogen, despite the fact that immunization with a small peptide corresponding to that site reveals both the ability of the site to bind to MHC molecules of the animal in question and the presence of a T-cell repertoire specific for that site. The antigenic site is not destroyed by processing, since it can be presented by the same F1 APC to T cells of another MHC type. Similarly, cross-reactivity between homologous epitopes of related proteins may occur at the peptide level even though the native proteins do not crossreact for the same T-cell clone. Since these events occur with monoclonal T cells, they cannot be due to suppressor cells specific for other sites on the native molecule. The best explanation is that the products of natural processing of the protein are larger than the peptides corresponding to the minimal antigenic sites, and contain hindering structures that interfere with binding to some MHC molecules and not others, or to some T-cell receptors and not others. Thus, antigen processing is a third factor that can lead to apparent Ir gene defects - in addition to MHC specificity and holes in the T-cell repertoire - and can significantly influence which antigenic sites are immunodominant.(ABSTRACT TRUNCATED AT 400 WORDS)
抗原加工包括蛋白质抗原在抗原呈递细胞内或表面必须经历的代谢过程，之后才能被T淋巴细胞识别。这些过程的一个主要目标似乎是使蛋白质解折叠，以暴露出埋藏在天然构象中的残基，天然构象旨在使其可溶于水。抗原呈递细胞通常通过蛋白质的蛋白水解切割来完成这项任务，但我们发现不进行蛋白水解的人工解折叠就足够了。解折叠的目的可能是使抗原位点的不同面同时与T细胞受体和抗原呈递细胞上的MHC分子结合，或与抗原呈递细胞膜上的其他结构相互作用。这种对解折叠的要求似乎适用于从小肽到大多聚体蛋白的所有物质。我们发现抗原加工的方式和产生的片段结构会极大地影响抗原位点的可用性。例如，当天然蛋白质用作免疫原时，一些抗原位点不被识别，尽管用对应于该位点的小肽进行免疫显示该位点具有与所讨论动物的MHC分子结合的能力以及存在针对该位点的T细胞库。抗原位点不会因加工而被破坏，因为它可以由相同的F1抗原呈递细胞呈递给另一种MHC类型的T细胞。同样，相关蛋白质同源表位之间的交叉反应性可能在肽水平发生，即使天然蛋白质对同一T细胞克隆不发生交叉反应。由于这些事件发生在单克隆T细胞中，它们不可能是由于对天然分子上其他位点具有特异性的抑制细胞所致。最好的解释是蛋白质天然加工的产物大于对应于最小抗原位点的肽，并且包含阻碍结构，这些结构会干扰与某些MHC分子而非其他MHC分子的结合，或与某些T细胞受体而非其他T细胞受体的结合。因此，抗原加工是除了MHC特异性和T细胞库中的空缺之外，可导致明显Ir基因缺陷的第三个因素，并且可显著影响哪些抗原位点是免疫显性的。（摘要截短至400字）
