Appendix L. 
351 
engraftment in the absence of immunosuppression despite 
acquisition of surface HLA molecule expression. These observations 
may have significant impact on the emerging field of regenerative 
medicine. 
2. IMMUNOBIOLOGY OF ORGAN TRANSPLANTATION 
The Human Leukocyte Antigens (HLA) 
Differences between individuals which enable immune recognition of 
non-self from self are principally due to the extreme polymorphism of 
genes in the Major Histocompatibility Complex (MHC) on 
chromosome 6 in man which encode the cell surface HLA molecules. 
These molecules are cell surface glycoproteins whose biologic 
function is to bind antigenic peptides (epitopes) derived from 
viruses, bacteria, or cancer cells, and present them to T cells for 
subsequent immune recognition. Each HLA gene includes a large 
number of alleles and the peptide binding specificity varies for each 
different HLA allele. The 1996 WHO HLA Nomenclature Committee 
report lists more than 500 different HLA class I and class II alleles. 
Crystallographic x-ray studies have demonstrated that the 
hypervariable regions encoded by polymorphic regions in the alleles 
correspond to HLA binding pockets which engage specific "anchor" 
residues of peptide ligands. One HLA molecule will recognize a 
range of possible peptides, whereas another HLA molecule will 
recognize a different range of peptides. Consequently, no two 
individuals will have the same capability of stimulating an immune 
response, since they do not bind the same range of immunogenic 
peptides. It is estimated that >99% of all possible peptides derived 
from foreign antigens are ignored by any given HLA molecule. Since 
in the absence of HLA polymorphism a large number of immunogenic 
peptides would not be recognized, the extensive HLA polymorphism 
in the population reduces the chance that a given virus or bacterium 
would not be recognized by a sizable proportion of the population, 
reducing the likelihood of major epidemics or pandemics. 
T Cell Recognition Of Antigen Presented By HLA Molecules 
Since HLA molecules regulate peptide display to and activation of 
the immune system, considerable effort has been devoted to 
understanding the molecular basis of peptide-HLA interactions. 
These issues are important for defining the biology of T cell antigen 
recognition and the properties of a protein that make it immunogenic 
or non-immunogenic. Specific antigen recognition by T cells is 
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