Antigen Processing: A Reevaluation

Abstract

In immunology, like in many other sciences, there are certain articles of faith in which we believe mostly because they seem to make sense. Antigen processing, the belief that antigen is taken up by cells, internalized, degraded, and then reexpressed on the cell surfaces¹, is one such article of faith. It makes sense because it is known that things go into and come out of cells and because the native antigen — a bacterium, a virus, or a soluble protein — seems too large a morsel to wet the appetite of a T cell. In addition, if one believes that antigen-presenting cells select, via their major histocompatibility complex (Mhc) molecules, which antigenic determinant will be recognized by the T cells, it makes sense that the antigen is broken down into pieces and the fragments then presented separately from each other by the antigen-presenting cell (APC). Yet, there is no direct evidence that cells process antigen in this fashion. Nobody has ever seen a protein globule disappear in a cell and then come out again shattered into fragments that can associate with the cell-surface Mhc molecules to be recognized by T lymphocytes. There is, to be sure, some circumstantial evidence that such events occur and as long as there were no contradictory data, it seemed reasonable, indeed, to believe that antigens need to be processed before they can be presented to T cells. However, contradictory evidence has recently been obtained and so it seems that the time has come to evaluate critically the antigen processing hypothesis. This article is a modest attempt to do just that.