four possible haplotypesac, ad, bc, and bdcan be found in the offspring.

It can be calculated that 25 percent of the offspring will have identical HLA haplotypes, 50 percent will share one HLA haplotype, and 25 percent will share no HLA haplotypes. An important corollary is that a parent and child can share only one haplotype, making an identical match between the two unlikely. It should also be apparent that uncles, grandparents, and cousins are very unlikely to have identical haplotypes with any given child. These are important factors when looking for a well-matched organ or blood donor. The HLA phenotype, then, represents the surface markers or antigens detected in histocompatibility testing of a single individual. The HLA genotype represents the association of the alleles on the two chromosomes as determined by family studies, and the term haplotype refers to the allelic makeup of a single chromosome, illustrated in Figure 224.

HLA Gene Products Structure

HLA gene products are globular glycoproteins, each composed of two noncovalently linked chains. Class I (HLA-A, HLA-B, and HLA-C) molecules consist of a heavy chain with a molecular weight of 45,000 daltons associated noncovalently with _2-microglobulin, a nonpolymorphic protein of 12,000 dalton molecular weight found in serum and urine. The heavy chain folds into three domains and is inserted through the cell membrane via a hydrophobic sequence.17 Class II (HLA-DR, HLA-DQ, and HLA-DP) molecules consist of two similar-sized chains of a molecular weight of 33,000 (_) and 28,000 () daltons associated noncovalently throughout their extracellular portions. In these molecules, both chains are inserted through the membrane via hydrophobic regions. The extracellular portions of these chains fold into two domains.18,19 Class I molecules are present on all nucleated cells, dendritic cells, and platelets, whereas class II molecules have a much more restricted distribution. They are found only on B lymphocytes, activated T lymphocytes, macrophages, monocytes, and endothelial cells. Although class I and class II molecules have some obvious structural differences, they are thought to be very similar in overall three-dimensional configuration (Fig. 225). Class I and class II molecules are also alike in that most of the polymorphism is expressed in the portion of the molecule farthest from the cell membrane.
20

Early structural models of class I molecules indicated that the _-1 and _-2 domains consisted of stretches of amino acids that were arranged into helical structures rather than sheets typical of globular proteins. The crystallography studies of Bjorkman and colleagues21 elucidated the three-dimensional structure of the class I, HLA-A2 molecule. The _1 and _2 domains form a platform overlaid by two