Chapter 3 – The Major Histocompatibility Complex

In the 1930’s Peter Gorer, working at the Jackson Laboratory in the US, discovered that tumours could be transplanted between mice which shared a group of alleles which he named Antigen II. Mice with different Antigen II alleles rejected the transplanted tumours. Soon after, George Snell demonstrated in a series of mouse crossing experiments, that the transplantability of tumours was controlled by a small number of loci and he named the principle one of these the Major Histocompatibility or H locus. Gorer and Snell had in fact identified the same system and in collaboration named the system H-2 (H for histocompatibility and 2 for antigen II). This is the first early picture of what later came to be called the Major Histocompatibility Complex (MHC) present not just in mice but in many other vertebrates including humans where it is also known as the Human Leukocyte Antigen (HLA) system. The primary role of the HLA molecules is to present pathogen derived peptides to T cells thereby eliciting a T cell mediated adaptive immune response. The T cell recognises both the HLA molecule and the peptide it presents, distinguishing self derived peptides from foreign peptides. This ability to restrict the T cell response, distinguishing self from foreign and permitting an immune response to be mounted against the foreign makes HLA antigens the main immunological barrier to transplantation, necessitating HLA matching for solid organ and stem cell transplantation.

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