Human Leukocyte Antigen

The Major Histocompatibility Complex (MHC) comprises a number of genes that occur in many species. The encoded proteins help the adaptive immune system to tell the body's own proteins apart from those of pathogens such as viruses, bacteria, and protozoans. In humans, MHC proteins are encoded by the Human Leukocyte Antigen (HLA), a group of more than 200 genes located closely together on the short arm of chromosome 6.

Human Leukocyte Antigen (HLA) on Human Chromosome VI

MHC class I complexes are heterodimers consisting of a polymorphic α heavy chain and an invariant β₂ microglobulin chain (β₂m). Genes encoding the α heavy chain are situated within the MHC class I locus whereas the β₂ microtubulin genes are typically found outside of this region. The α heavy chain is structurally separated into three N-terminal extracellular domain, α₁, α₂, and α₃, a transmembrane domain, and a short C-terminal cytoplasmic region. Domains α₁ and α₂ form the peptide-binding groove where peptides from endogenously synthesized proteins are presented to CD8+ cytotoxic T cells. Covalently linked β₂m serves as a conformational chaperone enabling peptide binding.

antibodies-online offers high quality recombinant class I HLA proteins and corresponding antibodies. Our HLAs are produced in mammalian cell cultures as recombinant, truncated, soluble proteins, in complex with β₂m.

Our Popular HLA Class I Antibodies

Our Popular HLA Class I Proteins

MHC class II complexes are heterodimers consisting of two polymorphic chains, α and β, each with two domains. The corresponding genes for both subunits are situated within the MHC class II locus. The peptide-binding groove in MHC class II complexes is formed by domains α₁ and β₁ and peptides are derived from exogenous proteins and presented to CD4+ helper T cells. Upon binding of the epitope by naïve helper T cells, they are primed and undergo polarization into effector or memory Th or Treg cells.

antibodies-online offers high quality recombinant class II HLA proteins. Our HLAs are produced in mammalian cell cultures as recombinant, truncated, soluble antigens, as zipper-stabilized heterodimers.

Our Popular HLA Class II Antibodies

Our Popular HLA Class II Proteins

A third cluster of HLAs (MHC class III) between the class I and class II MHC genes encodes components of the complements system and is not involved in the adaptive immune response.

HLA Nomenclature

Each HLA allele has a unique name consisting of the gene name, separated by an asterisk from up to four sets of digits which are separated by colons. Allele names have at least four digits, corresponding to the first two sets designating the allele group and the specific HLA protein. The third and fourth set of digits indicate changes in the DNA sequences in the coding and non-coding regions respectively, that do not influence the amino acid sequence of the protein. They are only assigned if necessary.

HLA typing refers to the process of identifying the specific alleles present at HLA gene loci, which encode cell surface proteins responsible for immune system regulation. Accurate HLA typing is essential for determining compatibility between donors and recipients in organ transplantation and for understanding the genetic basis of various diseases and drug responses.2-field reporting is a HLA typing method that identifies alleles based on their protein sequence differences. This reporting format provides information on the first two fields of the allele designation, i.e. the allele group and the specific HLA protein. 2-field reporting does not include any information about the corresponding DNA sequence. 4-field reporting on the other hand includes all four fields of the HLA allele, including its nucleotide sequence. In a clinical setting, 2-field reporting can sufficiently describe disease associations of particular HLA types or donor-recipient compatibility in a transplantation. 4-field reporting adds additional information which can be in a research setting, e.g. genomics studies.

HLA in Infectious Diseases

Classical class I and class II MHC are leading candidates for infectious disease susceptibility. Many observations point to a major role in determining susceptibility to viral infections. Individuals with the allele HLA-B*46:01 for example have been shown to have the fewest predicted binding peptides for SARS and SARS-CoV-2. A different allele, HLA-B*15:03, shows the greatest capacity to present highly conserved SARS-CoV-2 peptides that are shared among common human coronaviruses, suggesting it could enable cross-protective T-cell based immunity.These observations point towards a potential influence of different HLA composition - the haplotype - in the situations such as the SARS-CoV-2 pandemic. Association of various HLA haplotypes with SARS-CoV-2 susceptibility and the course of COVID-19 could allow strategizing prevention, treatment, vaccination, and optimizing clinical approaches.

Peptide-Free HLA Molecules

Despite the influence of the HLA haplotype, the main determinant of HLA-specificity is the presented peptide. Peptide-free MHC proteins are utilized in various research areas such as structural studies and T cell receptor engineering, to identify potential new drug candidates, in vaccine development, and to explore the functional aspects of MHC molecules. However, MHC molecules are generally not stable in the peptide-free state and must be stabilized.

antibodies-online offers assembled and stabilized peptide-free MHC class I complexes in monomeric and tetrameric formats expressed in HEK-293 cells.

References

Dr. Stefan Pellenz, PhD

Product Manager at antibodies-online.com

Goal-oriented, time line driven scientist, proficiently trained in different academic institutions in Germany, France and the USA. Experienced in the life sciences e-commerce environment with a focus on product development and customer relation management.

Go to author page