B*3503, are more likely to progress to AIDS compared to individuals carrying other B*35 subtypes, B*3501 and B*3508 (20).

Allorecognition

Nobel prize winning studies by Drs. Snell, Dausset, and Benacerraf identified molecules that play a predominant role in the rejection of transplanted tissue (4, 13, 24, 76). Tissues from one individual transplanted into a patient are detected as foreign by the immune system. This recognition process is controlled in part by the major histocompatibility molecules, HLA. In hematopoietic stem cell transplantation, the immune response may be directed against the graft (patient’s immune system rejecting the graft) or against the recipient (donor’s immune cells rejecting the patient’s cells, termed graft versus host disease).

T lymphocytes can respond to foreign HLA molecules either by direct recognition of the foreign HLA molecule or by indirect recognition of a self HLA molecule presenting a peptide from a foreign HLA molecule (19,78). Polymorphic molecules other than HLA may stimulate the immune system when presented by HLA molecules and are termed minor histocompatibility antigens (14). The impact of these “minor” responses on transplant is not yet clear. Natural killer (NK) cells have also been implicated in allorecognition responses, activated by missing HLA molecules (64). HLA alloantibodies synthesized by B lymphocytes have been associated with graft rejection (62). Although each of these immune cell types may affect transplant outcomes, current evidence suggests that T lymphocytes play the dominant role.

Since most HLA alleles encode proteins which differ from one another in the amino acid sequence of the antigen binding domains, most are theoretically capable of stimulating alloreactive T cells.

SOURCES OF HEMATOPOIETIC STEM CELL DONORS

Related Donors

In order to avoid allorecognition, physicians attempt to identify hematopoietic stem cell donors who are “HLA compatible” with their donors. Any two children in a family have a one in four chance of receiving the same two HLA gene-bearing chromosomes from their parents. Thus, within the United States, about 30 percent of patients identify an HLA compatible family donor. The remaining individuals must seek a histocompatible unrelated donor through registries of adult volunteer donors or through cord blood banks.



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