T-cell education towards self and non-self HLA: an overview of HLA-DP.

Abstract

An overview is presented of the role of the various Human Leukocyte Antigens (HLA) in the immune response with special emphasis on HLA-DP. In recent years, almost all HLA genes have been studied regarding their molecular and biochemical properties, with the exception of HLA-DP. HLA-DP is a HLA class II molecule that has long be regarded as fairly unimportant, and minimal research has gone into illuminating its molecular and biochemical properties. However, recent results have shown that HLA-DP might be more important than previously anticipated. This overview summarizes the current knowledge on HLA-DP, and its role in T-cell selection in the thymus. In addition, suggestions for future research are presented.

The genes coding for the HLA-DP molecule, HLA-DPA1 and HLA-DPB1, were already discovered in 1987, yet there are no details on HLA-DP expression, except for a commonly sheared mechanism amongst HLA class II genes. It has been shown that HLA-DP cannot be simply compared to other HLA class II molecules when it comes to localization, assembly, trafficking or peptide presentation. HLA-DP has been found to be involved in many different immune related disease, such sarcoidosis, juvenile arthritis, Graves’ disease, graft versus host disease, hard metal lung disease and chronic beryllium disease. Various studies show that HLA-DP plays an important role in either the initiation or progression of these diseases. Within HLA-DP a special role seems to be present for the DPB1*0201 allele, which has been associated with multiple immune diseases. The consequences of this knowledge will likely influence how we treat these immune diseases. In addition, HLA-DP may also play a role in transplantation disease. As of today, HLA-DP matching is not standard before performing an organ transplantation. However, the new insights in the role of HLA-DP might well change that for the future. In conclusion, although HLA-DP has long been largely ignored, it is now becoming clear that HLA-DP may well be a very important factor for both for (auto) immune and transplantation diseases.