Ribosomal versus non‐ribosomal cellular antigens: factors determining efficiency of indirect presentation to CD4+T cells

Abstract

Proteins released from dying cells can be taken up and presented by antigen-presenting cells (APC) to T cells. While the presentation of such self antigens may lead to beneficial anti-tumour responses, in autoimmune disease it leads to pathological immune responses. The sub-set of self proteins targeted in autoimmune disease is circumscribed, and certain cellular components such as ribonucleoprotein (RNP) complexes are often targeted. Although explanations for this antigen selectivity have been proposed, there has been little direct testing of these hypotheses. We and others previously showed that ribosomal proteins, targeted in autoimmune disease, are also targets of anti-tumour T-cell responses. We asked whether particular properties of ribosomal proteins such as incorporation into RNP complexes or sub-cellular localization enhance ribosomal protein presentation by APC to CD4(+) T cells. Ribosomal protein antigens within purified intact ribosomes or free of the ribosomes were equally well taken up and presented by APC, demonstrating that inclusion of ribosomal proteins into an RNP complex does not confer an advantage. However, antigens localized to ribosomes within apoptotic cells were less efficiently taken up and presented by APC than the same antigens localized diffusely throughout the cell. This suggests that presentation of ribosomal proteins is somehow down-regulated, possibly to facilitate presentation of other less-abundant intracellular proteins. Consequently, the explanation for the frequent targeting of ribosomal proteins by both autoimmune and anti-tumour T-cell responses is not at the level of uptake from apoptotic cells and must be sought elsewhere.