(click here for detailed description of structure and function of MHC molecules and MHC typization tools

HLA-B and HLA-C alleles always maintain the additional "w" to distinguish them from the loci for complement factors B and C2 and C4, respectively, which are located in the MHC region, too. Also D alleles (now renamed DR) were once termed with the additional "w" to distinguish them from the locus for the complement factor D.

Serological nomenclature :

• HLA-( _ ( _ _ ) : locus (and sublocus of protein chain for class II only))(eventual paralogous gene)*( _ _ : type / serological group defined looking for microcytotoxicity in serological assays using mAb or sera from multiparous females (immunized by microchimerism))
• types defined with one-way heterologous mixed lymphocytary reaction (MLR) are marked with an additional "w" (for workshop) after the locus :
• serologically defined haplotypes are termed according to the detected type. Staining with HLA tetramers provides a means for identifying, quantifying, and isolating HLA-specific B cells^ref. The phenotype of HLA-specific B cells reflects current or historic sensitization to HLA and may reflect inherent differences between groups defined by race and/or gender. The frequencies of HLA-specific B cells may predict patients at risk for production of donor-specific antibody after transplantation^ref
• supertypes are group of types presenting at least a shared epitope. E.g. :
• HLA-A1 supertype
• HLA-A2 supertype
• HLA-A3 supertype
• HLA-A24 supertype
• HLA-B7 supertype
• HLA-B27 supertype
• HLA-B44 supertype
• HLA-B58 supertype
• HLA-B62 supertype
• HLA-DRw52 supertype (including HLA-DR3, HLA-DR5, HLA-DRw6, and HLA-DRw8 types) has nowadays been proved to correspond to HLA-DR ab₃ molecule
• HLA-DRw53 supertype (including HLA-DR4, HLA-DR7, and HLA-DR9) has nowadays been proved to correspond to HLA-DR ab₄ molecule

Molecular nomenclature :

• HLA-( _ ( _ _ ) : locus (and sublocus))(eventual paralogous gene)*( _ _ : type / allele group defined as a group of closely-related alleles at a locus)(_ _ : subtype / specific allele defined by DNA hybridization)(_ : samesense SNP in cds detected with DNA sequencing)(_ _ : SNP in intron or flanking region)( _ : expression level (N = no expression ; L = low expression ; no letter = normal level of expression)
• e.g. HLA-DRB4*0103102N

• low resolution : samples typed at the allele group level
• intermediate resolution : samples typed to a subset of alleles. E.g. DRB1*15(01,03,06)
• high resolution : samples typed to the allele level

Notes :

• since the HLA-A and HLA-B loci were discovered first they do not share type designations
• serological splits are sometimes written as broad sero name(split) or split(broad sero name)

HLA allele nucleotides are numbered based upon an archetypal cDNA sequence : that means new alleles are aligned with the archetype even if they have small insertions and deletions.

locus	DRB1/3/4/5	DPB1	DQA1	DQB1	A	B	Cw
archetype	DRB1*0101	DPB1*01011	DQA1*0501	DQB1*0501	class I cons.	class I cons	class  I cons.
start	1	1	-69	1	1	1	1
exon 1	13	13	13	13	73	73	73
exon 2	283	277	262	283	343	343	343
exon 3	565	559	544	565	619	619	619
exon 4	676	670	699(end)	676	895	895	895
exon 5	700	690(end)		703	1015	1015	1015
exon 6	714(end)			714(end)	1057	1057	1057
exon 7					1096	1096	1096
exon 8					1101(end)	1101(end)	1101(end)

The strongest linkage disequilibria are between :

• B-Cw
• DRB1-DRB3/4/5

• monozygosis :
• absent in that haplotype (eg DR10-DQ5 class II haplotype lacks a DRB3/4/5)
• gene deletion
• (true) homozygosis, to be proved by family studies
• pseudogene : null alleles cannot be detected serologically
• technical limitations :
• some Cw antigens cannot be detected serologically
• due to high paralogy : apparent homozygosis (serology is unable to split the 2 alleles)

An unrelated donor is considered when a suitable human leukocyte antigen (HLA) identical sibling cannot be found in the family. It is known that the outcome of BMT from unrelated donors is inferior to that from HLA identical siblings which suggests undetected mismatching of HLA genes and/or mismatching in non-HLA polymorphic genes in the major histocompatibility complex (MHC)^{ref1, ref2, ref3}. HLA identical siblings are matched throughout the MHC, including non-HLA polymorphic genes. Transplantation between these related pairs suggests that matching MHC haplotypes in identical siblings provides a superior outcome. Unrelated donors who are HLA matched with their patients and matched for non-HLA polymorphic genes may share the entire MHC region and be equivalent to HLA identical siblings. For MHC haplotype matching, the MHC block matching technique was developed to match for genomic blocks rather than for individual HLA loci and to enable the identification of donors and recipients who are matched for HLA and non-HLA sequences in the MHC equivalent to HLA identical siblings. MHC block matching is based upon the premise that the MHC includes the following polymorphic blocks^{ref1, ref2, ref3}: the alpha block corresponding to a gene cluster around HLA-A, the beta block corresponding to a gene cluster around HLA-B and HLA-Cw, the gamma block corresponding to a gene cluster around Bf and C4, and the delta block corresponding to a gene cluster around HLA-DR and DQ.
One of these blocks, the beta block, spans about 300 kb^ref and contains the immunologically relevant HLA-B, HLA-Cw, MICA, and MICB genes. Retrospective and prospective studies have shown that matching donors and recipients for non-HLA DNA sequences in the MHC (beta and delta block matching) can result in improved patient survival and less severe acute graft versus host disease (GVHD)^{ref1, ref2, ref3, ref4}. It is possible that improved survival with MHC block matching may be attributed to matching of non-HLA genes such as MICA and MICB whose influence on outcome is not clear^{ref1, ref2}.
MICA and MICB are highly polymorphic with at least 59 alleles for MICA (considering polymorphisms at both extracellular and transmembrane domains) and 19 alleles for MICB. MICA and MICB are located 46.4 and 141.2 kb centromeric to HLA-B, respectively^{ref1, ref2, ref3}. Recent studies have shown that the highly polymorphic MIC antigens are expressed in transplanted organs and may cause early graft rejection^{ref1, ref2}. Thus, the polymorphisms of MICA and MICB may be involved in allogeneic BMT and GVHD^ref. Although it is known that the MIC gene products are ligands of NKG2D^ref, an activating receptor on several immune cells, the actual roles of MICA and MICB in bone marrow transplantation have not yet been demonstrated. However, it is evident that the MHC beta block marker is also a marker for the MICA and MICB genes^ref.

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