Of course the system cannot be too selective lest it fail to react at all. Another possible adaptive function for MHC selectivity is to allow some self- proteins to be tolerated by the immune system even though they cannot be presented during thymocyte processing. Certain signal proteins, for example, might be inappropriate for expression in the thymus. Since different signal proteins tend to be homologous it is only necessary for the sampling process to ignore those portions of the protein that vary from versions that can be expressed in the thymus. Alternately the thymus could even express non-functional variants of signal proteins for the sole purpose of deleting reactive thymocytes.
Selectivity eases training.
To show the impact of MHC selectivity on training reliability , we assume a simple model of training wherein each thymocyte is repeatedly presented with self-peptides randomly sampled by the organism's MHC allotypes. To be sure a thymocyte is not self reactive, it must be presented with all fS self- peptides. The counter pressure to greater MHC selectivity is insuring that inappropriate peptides, such as viral protein fragments, are sampled adequately. We promised above to consider whether code word space large was enough, i.e. whether the length of peptides observed to bind to MHC protein is large enough to allow distinction between self and non-self. To do this we must first estimate how many different protein fragments can occur in normal proteolysis.