HLA class I function as part of the adaptive immune system and play a vital role in recognizing self from non-self as well as providing protection against viruses and tumors. In a healthy person HLA class 1 bind degraded cytosolic self-proteins and then transport these fragments to the cell membrane where they present to CD8+ T lymphocytes. When the presented peptide is of foreign origin, such as peptide derived from a virus-infected cell, the CD8+ T cell works to eliminate the infected cell.

MHC class 1 presenting self-proteins also serves as an inhibitory signal to NK cells; this prevents NK killing of healthy cells.

HLAs are identifiable via multiple different types of detection methods.

Molecular Testing

Sequence-specific primer polymerase chain reaction: this method makes use of various primers that are complementary to specific HLA DNA sequences. The DNA is plated into a multi-well plate with different primers. If the DNA extracted from that cell is complementary to the primer, it will be amplified, and the product can be run on a gel via electrophoresis. The band can be identified as a particular primer and matched to candidate HLA alleles that are known.[8]

Sequence-specific oligonucleotide probes

One way to detect the high polymorphism seen in these genes is via polymerase chain reaction paired with sequence-specific oligonucleotides. This method involves amplifies the gene via PCR and then probing DNA with a fluorescent tag. The HLA type is determined using known HLA alleles as a reference, and that gene may undergo sequencing.[9][8]

Direct DNA sequencing

Another technique is to use sanger sequencing or next-gen sequencing to sequence the entire gene of a specific HLA variant after amplification via PCR. Once the sequence is known, it can be compared to previously published know HLA alleles.[8]

Serological Testing

Serological testing generally uses a recipient's lymphocytes obtained from their sera and incubated with anti-sera containing antibodies against various HLA class 1 subtypes. The solution is then incubated with rabbit sera, providing a source of complement; a dye is also added, which allows the identification of dead cells. This assay progresses serially with different HLA antibodies put into each well of a tray. Through the elimination of those wells with a positive result allows for the determination of the HLA type. This method provides a relatively quick and easy way to determine general subtypes of HLA's present but does not offer an in-depth analysis of the true molecular identity of the HLA's. This method is less common today because of its inability to detect small changes in HLA types that may make an immunological difference and cause a transfusion reaction.[10][8]

Antibody Testing

Cytotoxic cell-based antibody testing can also be an effective way to measure the recipient's risk of having a positive crossmatch. In this method, a set of 30-40 donor cell lymphocytes are mixed with dye and complement with the serum of the recipient. If the serum of the recipient contains a high enough level of HLA specific antibodies against a particular donor lymphocyte complement will be activated, the cell will die, and the dye will be taken up, and that well in the plate will be visually identifiable as a positive result. This test yields a value known as a percentage panel reactive antibody. Its result measures the recipient's risk of a positive crossmatch in a similar population of donors. This test does lack the ability to take race and different HLA frequencies in a population into account, weakening its value.[8]

Transplant rejection remains one of the most clinically relevant issues surrounding the HLA class 1 molecule. Proper identification of the donor and recipient’s HLA status is imperative to prevent transplantation reactions. Continuing education on the different types of serological, molecular, and cellular tests available to clinicians, and their proper use and healthcare professionals must learn how to interpret them.

Spondylosis Ankylosis

Research has shown a strong correlation between HLA B27 and ankylosing spondylitis. Among those with the HLA B27 allele, 5 to 6 percent develop ankylosing spondylitis (AS).[11] AS is a seronegative spondyloarthropathy, which leads to progressive stiffness of the spine and sacroiliac joints. This stiffness is the result of improper bone deposition leading to fused vertebrae. The exact role of HLA B27 in AS is still unknown.[12]

Behcet Disease

Research has found the HLA B51 allele to be the single greatest risk factor in developing Behcet disease. Behcet disease is an autoinflammatory condition that results in normally immune-privileged sites such as the brain, eye, and joints to become infiltrated with neutrophils. The link between the pathogenesis of Behcet disease and HLA B51 is still unclear. More research is needed to ascertain the true connection between the HLA B21 allele and Behcet disease. Researchers postulate that it could be due to antigen presentation to CD8 + cell or HLA B51’s interaction with NK receptor KIR3DL1.[13]

Psoriasis

Psoriasis, an autoimmune condition, is highly linked to specific HLA alleles. HLA A01, HLA A02, B13, B17 B39, B57, Cw06, Cw07 are all HLA class one molecules associated with psoriasis. The role of HLA in psoriasis is currently unknown.[14]

Birdshot Chorioretinopathy

Birdshot chorioretinopathy, a form of posterior uveitis, correlates with HLA A29, with 85 to 97.5 percent of those diagnosed carrying the allele.[15]

HIV

HLA B27, B51, HLA C06, and HLA B5701 all confer protection against HIV infection. The reason appears to be that the peptides presented by these alleles are structurally resistant to mutation. Another idea is that those CD8 positive T cells that interact with these specific alleles have higher functionality in riding the body of HIV infected cells.[15]