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HLA-DR subregion 336 HLA tissue typing
HLA-DR1 histocompatibility antigen.
molecules. Monoclonal antibodies are now used to recognize
certain antigenic determinants shared by various molecules
bearing the same HLA typing specificity. Monoclonal
antibodies have been employed to recognize specific class II
alleles with disease associations.
HLA-DR subregion
The site of one HLA-DRA gene. Although the DRB gene
number varies with DR type, the usual number is three DRB
genes, termed DRB1, DRB2, and DRB3 (or DRB4). The
DRB2 pseudogene is not expressed. The DR α chain encoded
by the DRA gene can unite with products of DRB1 and
DRB3 (or DRB4) genes that are the DR β-1 and DR β-3 (or
DR β-4) chains. This yields two separate DR molecules, DR
αβ-1 and DR αβ-3 (or DR αβ-4). The DRβ chain determines
the DR antigen (DR type), as it is very polymorphic, whereas
the DRα chain is not. DR αβ-1 molecules carry DR specificities
DR1–DRw18. Yet, DR αβ-3 molecules carry the DRw52,
and the DR αβ-4 molecules carry the DRw53 specificity.
HLA-E
Human leukocyte antigen (HLA) class I nonclassical molecule.
Relatively invariant human MHC class I molecules
that serve as ligands for NK cell receptors.
HLA-F
Human leukocyte antigen (HLA) class I nonclassical molecule.
Believed to be a peptide-binding molecule that may
reach the cell surface where it would be capable of interacting
with LIR1 (ILT2) and LIR2 (ILT4) receptors, thereby
altering the activation thresholds of immune effector cells.
A predominantly empty, intracellular, TAP-associated
MHC class Ib protein with a restricted expression pattern.
HLA-G
HLA-G either is nonpolymorphic or has very limited
polymorphism. It is a nonclassical (class Ib) major histocompatibility
complex (MHC) molecule expressed in
immune-privileged tissues. It is a class I HLA antigen
with extensive variability in the α-2 domain. It is found on
trophoblasts (i.e., placenta cells and trophoblastic neoplasms).
HLA-G is expressed only on cells such as placental
extravillous cytotrophoblasts, and choriocarcinoma that fail
to express HLA-A, -B, and -C antigens. HLA-G expression
is most pronounced during the first trimester of pregnancy.
Fetal trophoblasts do not express the class Ia MHC molecule’s
HLA-A and HLA-B, allowing the fetus to escape the
maternal T cell response. Evidence suggests that HLA-G
protects the fetus from attack by natural killer (NK) cells,
macrophages, and monocytes by interacting with the inhibitory
receptors on leukocyte immunoglobulin-like receptor 1
(LIR-1 or ILT-2), leukocyte immunoglobulin-like receptor 2
(LIR02 or ILT-4), and killer immunoglobulin-like receptor
2DL4 (KIR2DLA). Trophoblast cells expressing HLA-G at
the maternal–fetal junction may protect the semiallogeneic
fetus from “rejection.” Prominent HLA-G expression suggests
maternal immune tolerance. HLA-G exerts tolerogenic
functions involved in transplant acceptance as well as
in tumoral and viral immune escape.
HLA-H
A pseudogene found in the major histocompatibility
complex (MHC) class I region that is structurally similar
to HLA-A but is nonfunctional due to the absence of a
cysteine residue at position 164 in its protein product and
the deletion of the codon 227 nucleotide.
HLA complex
Alternate name for human major histocompatibility complex
(MHC).
HLA locus
The major histocompatibility locus in humans.
HLA nonclassical class I genes
Genes located within the major histocompatibility complex
(MHC) class I region that encode products that can associate
with β 2 microglobulin; however, their function and tissue
distribution are different from those of HLA-A, -B, and
-C molecules. Examples include HLA-E, -F, and -G. Only
HLA-G is expressed on cell surfaces. Whether these HLA
molecules are involved in peptide binding and presentation
like classical class I molecules remains uncertain.
HLA oligotyping
A recently developed method using oligonucleotide probes
to supplement other histocompatibility testing techniques.
Whereas serological and cellular methods identify phenotypic
characteristics of human leukocyte antigen (HLA) proteins,
oligotyping defines the genotype of the DNA that encodes
HLA protein structure and specificity. Thus, oligotyping can
identify a DNA type even when a failure of expression of
HLA genes renders serological techniques ineffective.
HLA tissue typing
The identification of major histocompatibility complex
(MHC) class I and class II antigens on lymphocytes by
serological and cellular techniques. The principal serological
assay is microlymphocytotoxicity using a microtiter
plate containing predispensed antibodies against human
leukocyte antigen (HLA) specificities to which lymphocytes
of unknown specificity plus rabbit complement and vital
dye are added. Following incubation, the wells are scored
according to the relative proportion of cells killed. This
method is employed for organ transplants such as renal
allotransplants. For bone marrow transplants, mixed lymphocyte
reaction procedures are performed to determine
the relative degree of histocompatibility or histoincompatibility
between donor and recipient. Serological tests have
been largely replaced by DNA typing procedures employing