Cytotoxic T lymphocytes against a soluble protein

Abstract

Thymus-derived (T) lymphocytes recognize antigen in conjunction with surface glycoproteins encoded by major histocompatibility complex (MHC) genes^1–3. Whereas fragments of soluble antigens are presented to T helper lymphocytes (T_H), which carry the CD4 antigen, in association with class II MHC molecules⁴, CD8-bearing cytotoxic T lymphocytes (CTL) usually see cellular antigens (for instance virally-encoded proteins) in conjunction with MHC class I molecules^5,6. The different modes of antigen presentation may result from separate intracellular transport: vesicles containing class II molecules are thought to fuse with those carrying endocytosed soluble proteins. Class I molecules, in contrast, can only pick up degradation products of intracellular proteins (see refs 7 and 8). This makes biological sense; during an attack of a virus, class I-restricted CTL destroy infected cells and class II-restricted T_H guide the humoural response to neutralize virus particles and toxins. But here we provide evidence that CTL specific for ovalbumin fragments can be induced with soluble protein, and that intracellular protein degradation provides epitopes recognized by these CTL. These findings suggest the existence of an antigen presenting cell that takes up soluble material and induces CTL.