Biomedical Engineering Reference
In-Depth Information
Chapter 10
The HLA and ABO Systems
in the View of Stem Cell Transplant
(HLA Typization: Choice of Donors)
Each problem that I solved became a rule which served
afterwards to solve other problems.
- Rene Descartes
The MHC is a large and stable region mapped to the short arm of the chromosome
6, encoding genes that have a lot of functions in immune and nonimmune response.
MHC includes regions for the well-known and the most polymorphic until now
discovered gene system, the human leukocyte antigen (HLA) genes. The extreme
polymorphism of the HLA system derives from the existence of multiple alleles at
several loci. It is estimated that more than 100 million different phenotypes can
result from all combinations of alleles in the HLA system [
1-
5
] . HLA genes are
autosomal with codominant expression, inherited regularly as a haplotype. Since
progeny receives one chromosome (haplotype) from each parent, four combinations
of haplotypes are possible in newborn. Seldom HLA genes show chromosome
crossover and these recombinants are then transmitted as new haplotypes to the
offspring. These genes contribute to the recognition of self and nonself, to the
immune response to antigenic stimulus, and to coordination of cellular and humoral
immunity. Discrimination of self from nonself is realized primarily through the
interaction of T lymphocytes with peptide antigens (epitopes presented by antigen
presented cells), but only when the T-cell receptor binds both an HLA molecule and
speci fi c antigenic peptide [
4-
6
] .
MHC genes are divided into three regions. The class I region encodes more than
18 HLA genes and pseudogenes. HLA-A, HLA-B, and HLA-C genes are respon-
sible for the corresponding A, B, and C antigens. Other class I genes (e.g., HLA-E,
HLA-F, HLA-G) encode different nonclassical HLA proteins with limited level of
polymorphism and expression. Several class I genes express nonfunctional proteins
or nonprotein antigens (such as lipids). Genes unable to express a protein product
are termed pseudogenes. The most centromeric on chromosome 6 is the class II
region, which contains the 17 known HLA genes and pseudogenes. In general,
