1. History and Overview -- 2. The MHC Genes -- 3. The Structure -- 4. The Function -- 5. Recognition by Immune Cells -- Appendix A: Useful Internet Addresses -- Appendix B: Computer Programs -- Appendix C: Abbreviations.

MHC Ligands and Peptide Motifs

ContextThe advent of single-cell polymerase chain reaction (PCR) has presented
the opportunity for combined preimplantation genetic diagnosis (PGD) and HLA
antigen testing. This is a novel and useful way to preselect a potential donor
for an affected sibling requiring stem cell transplantation.ObjectiveTo perform in vitro fertilization (IVF) and preimplantation HLA matching
combined with PGD for Fanconi anemia (FA).DesignDNA analysis for the IVS 4 + 4 A→T (adenine to thymine) mutation
in the FA complement C (FANCC) gene in single blastomeres,
obtained by biopsy of embryos, to identify genetic status and HLA markers
of each embryo before intrauterine transfer.SettingIn vitro fertilization programs at large medical centers in Chicago,
Ill, and Denver, Colo.ParticipantsA couple, both carriers of the IVS 4 + 4 A→T mutation in the FANCC gene with an affected child requiring an HLA-compatible
donor for cord blood transplantation.Main Outcome MeasuresDNA analysis of single blastomeres to preselect unaffected embryos representing
an HLA match for the affected sibling.ResultsOf 30 embryos tested in 4 IVF attempts, 6 were homozygous affected and
24 were unaffected. Five of these embryos were also found to be HLA-compatible,
of which 2 were transferred in the first and 1 in each of the other 3 cycles,
resulting in a pregnancy and birth of an unaffected child in the last cycle.ConclusionTo our knowledge, this is the first PGD with HLA matching, demonstrating
feasibility of preselecting unaffected embryos that can also be an HLA-compatible
source for stem cell transplantation for a sibling.

https://jamanetwork.com/journals/jama/articlepdf/193944/jbr00301.pdf

Preimplantation diagnosis for Fanconi anemia combined with HLA matching.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1399-0039.1997.tb02759.x

Nomenclature for factors of the HLA system, 1996

In this paper, we present a novel sequencing based typing strategy for the HLA-DRB1, 3, 4 and 5 loci. The new approach is based on a group-specific amplification from intron 1 to intron 2 according to the serologically-defined antigens. For this purpose, we have determined the 3' 500 bp-fragment of intron 1 and the 5' 340 bp-fragment of intron 2 of all serological antigens and their most frequent subtypes. We discovered a remarkably conserved diversity characterized by lineage-specific sequence motifs. This lineage-specificity of non-coding motifs in the 1st and 2nd intron offered the possibility to establish a clear serology-related amplification strategy. The method allows the complete analysis of the 2nd exon and the definition of the cis/trans linkage of sequence motifs by intron-mediated polymerase chain reaction (PCR)-based separation of the haplotypes in nearly all serologically heterozygous samples. In particular, the non-coding variabilities between the DR52-associated DRB1 groups made their independent amplification possible. Thus, compared to the standard procedures using exon-based amplification primers, the groups DR3, DR12, some DR13 alleles (1301, 1302) and the DR14 group could be amplified by specific primer mixes. The DR8 could be amplified with an individual primer mix not co-amplifying the DR12. The DR11 and DR13 did not show any individual motif in intron 1 or intron 2. In order to achieve a separate amplification, they had to be amplified by multispecific primer mixes (DR3/11/13/14; DR3/11/13 or DR11/13/14) excluding the other haplotype. Thus, exclusively the alleles in rare DR11,13 heterozygosities without a DRB1*1301 or 1302 could not be amplified separately. Fourteen primer mixes are used to amplify the specificities DR1-14, and 6 primer mixes for the specificities DR51-53. The sequence homology of the 3' end of intron 1 facilitated the application of only three different sequencing primers for all DRB alleles.

Sequencing of HLA class II genes based on the conserved diversity of the non-coding regions: sequencing based typing of HLA-DRB genes

The WHO Nomenclature Committee for factors of the HLA system met in Brighton in March 1995 at the joint meeting of the European Foundation for Immunogenetics and British Society for Histocompatibility and Immunogenetics to consider additions and revisions to the nomenclature of specificities defined by both molecular and serological techniques following the principles established in previous reports [l-121. sociated with the incorrect sequence is deleted. Names deleted on this basis are given in 2b. In some cases errors are suspected on the basis that they contain unexpected substitutions in normally conserved regions, but no material of the original sample is available for resequencing. As indicated in 2b, the names A*2401 and B*0701 have been deleted for this reason.

Nomenclature for factors of the HLA system, 1995.

A variety of reasons related to the HLA class I system has complicated the application of molecular approaches to HLA class I typing. Here we present a PCR-based HLA-A typing strategy considering the sequence variations of the two most polymorphic exons which allows complete subtyping of the HLA-A locus. The method is based on a sequence-specific amplification identifying the serologically defined HLA-A specificities. The PCR products generated by these group-specific primers bear the sequence information necessary for a postamplification specificity step. The primer pairs are located within one exon, either exon 2 or exon 3, which avoids amplification of polymorphic intron sequences allowing subsequent single-strand conformation polymorphism analysis and facilitating direct sequencing. Using this method we investigated 48 cell lines and 153 clinical samples. 23 PCR reactions are performed per individual for the assignment of the serological specificities A1-A80. The reproducibility was 100% in all cell lines and 85 clinical samples typed on two separate occasions. With the exception of 13 out of 231 possible serological combinations all homozygous and heterozygous combinations of A1-A80 can be distinguished by specific amplification patterns. Comparing the PCR based typing results with those of serology in 12% a discrepancy was found. Solid-phase sequencing or SSCP analysis of the group-specific PCR fragments allowed complete subtyping of the HLA-A locus. This strategy can identify all 48 HLA-A alleles based on the sequence variations of the 2nd and 3rd exon. 1128 homozygous and heterozygous allele combinations are possible for the HLA-A locus. Only 4 out of these 1128 allele combinations remained unresolved.

Complete subtyping of the HLA-A locus by sequence-specific amplification followed by direct sequencing or single-strand conformation polymorphism analysis

A novel hla-a24 allele (a*2405) identified by single-strand conformation polymorphism analysis and confirmed by solid-phase sequencing and isoelectric focusing

U. Hahn

Papers

Complete subtyping of the HLA-A locus by sequence-specific amplification followed by direct sequencing or single-strand conformation polymorphism analysis

A novel hla-a24 allele (a*2405) identified by single-strand conformation polymorphism analysis and confirmed by solid-phase sequencing and isoelectric focusing

Identification of a novel HLA-A33 subtype (A3303) and correction of the A3301 sequence.

A novel HLA‐A30 allele (A*3004) identified by single‐strand conformation polymorphism analysis and confirmed by solid‐phase sequencing

U. Hahn

Papers

Complete subtyping of the HLA-A locus by sequence-specific amplification followed by direct sequencing or single-strand conformation polymorphism analysis

A novel hla-a24 allele (a*2405) identified by single-strand conformation polymorphism analysis and confirmed by solid-phase sequencing and isoelectric focusing

Identification of a novel HLA-A33 subtype (A*3303) and correction of the A*3301 sequence.

A novel HLA‐A30 allele (A*3004) identified by single‐strand conformation polymorphism analysis and confirmed by solid‐phase sequencing

Identification of a novel HLA-A33 subtype (A3303) and correction of the A3301 sequence.