The Immunogenicity of HLA Class II Mismatches: The Predicted Presentation of Nonself Allo-HLA-Derived Peptide by the HLA-DR Phenotype of the Recipient Is Associated with the Formation of DSA

Figure 2

The indirect allorecognition pathway of allo-HLA class II by B cells and the presentation of self or nonself allo-HLA-derived peptide influence CD4+ cells helper function to lead to the formation of DSA. HLA mismatches can become immunogenic when they carry both a B cell epitope and a T cell epitope. B cell epitopes are located on the molecular surface of HLA, whereas T cell epitopes can be located anywhere, exposed or cryptic. B cells expressing a BCR specific for an allo-HLA can capture, internalize, and process the whole allo-HLA class II molecule and then present allo-HLA-derived peptides on the cell surface. Only when CD4+ cells recognize nonself antigenic determinants presented by B cells does the release of various cytokines promote B cell differentiation. This, in turn, may induce affinity maturation and Ig class switching, which eventually leads to the formation of DSA.