Introduction to Serotypes

What are Serotypes?

A serotype is defined by specific amino acid positions that determine how antibodies recognize and react with HLA molecules. Serotypes provide a systematic way to classify HLA alleles based on their molecular structure, offering more precise matching capabilities than traditional serological methods.

  • Specific amino-acid residues in the membrane-distal domain form the epitopes that antibodies recognize.
  • Different combinations of residues at these positions create distinct serological specificities.
  • This lets alleles that lack traditional serological typing data be classified, and supports more precise prediction of antibody reactions and transplant compatibility.

Many serotypes are named after a representative prototype allele: usually the lowest-numbered or most common two-field allele with that specificity, written without the colon (HLA-A*02:01 gives A-0201 while proposed, A0201 once WHO-accepted). Many other alleles map to the same serotype, so an allele's own number need not match the serotype it belongs to. Naming is not identical across loci: DRB3 and DRB5 specificities use DR52 and DR51 prefixes, respectively. Some serotypes retain conventional names, such as A1 and DR53.

The serological hierarchy

This classification organises HLA serological specificities from broad to split to serotype, in increasing resolution. The levels are nested, but may coincide where no further subdivision is defined.

Broad antigen

least specific

A9, B5, A10

The original, broadly defined specificity: one antibody reactivity that covers a whole family of related molecules.

Typing: Serology or low-resolution PCR (SSO/SSP)

Split antigen

more specific

often just called “the antigen”

A23, A24, B51

A narrower specificity that splits a broad into more defined reactivities.

Typing: Serology or intermediate-resolution PCR (SSO/SSP)

Serotype

most specific

A2301, A2403, B0702

The finest DEP-defined grouping in this classification, distinguishing alleles within a broad or split antigen. Assigning it requires allele-level sequence.

Typing: Allele-level sequencing (NGS, long-read / nanopore)

Naming: HATS marks candidate names with a hyphen (e.g., A-0201 before recognition as A0201).

Serotypes don't replace broads or splits

Broad, split and serotype are three resolutions of the same serological specificity. Each remains a valid serologic equivalent, so a laboratory can report whichever level its typing supports, and a serotype always rolls up to its split and broad.

Associated antigen

A formal WHO nomenclature category, not a general synonym for an allele's serological assignment. Many HATS serotypes now have associated-antigen designations, while others retain conventional antigen names or remain candidate specificities. Broad, split and serotype describe resolution here; WHO recognition is a separate consideration.

Recognition of a specificity's name does not mean that every allele mapped to it by HATS has a WHO assignment. HATS qualifiers describe the sequence match and assignment status, not official recognition. The IPD-IMGT/HLA explanation distinguishes WHO Assigned Antigen from HATS Assigned Antigen. WHO defines the nomenclature; the allele detail pages link to IPD-IMGT/HLA records for the official assignments.

WHO status on allele pages and tables

Whenever this site loads a new HATS release (checked nightly, see the About page), it also downloads the IPD-IMGT/HLA WMDA files of the IPD-IMGT/HLA release HATS was built from and reads, for every allele, WHO's unambiguous antigen, its possible antigens and its assumed antigen (rel_dna_ser.txt). That WHO antigen is compared with the HATS broad, split and serotype for the same allele, giving one of these statuses; a two-field allele carries the status of its full-field alleles. A serotype page also says whether the name itself is a current WHO antigen name (hla_nom.txt).

  • WHO assigned: WHO's unambiguous serological antigen for this allele is the HATS serotype.
  • WHO at split: WHO assigns this allele at the split level; HATS resolves it to a serotype within that split.
  • WHO at broad: WHO assigns this allele at the broad level; HATS resolves it to a serotype within that broad.
  • WHO differs: WHO's unambiguous antigen for this allele is outside the HATS broad, split and serotype.
  • WHO mixed: The full-field alleles under this two-field name carry different WHO antigens.
  • WHO assumed: WHO has no serological evidence for this allele; its antigen is assumed from the first field of the allele name.
  • WHO unknown: WHO records no corresponding antigen for this allele.
  • Null allele: WHO records the allele as not expressed, so it has no serological antigen.
  • No WHO value: The IPD-IMGT/HLA file carries no serological value for this allele.

WHO records evidence for a minority of alleles; most carry only an assumed antigen, which is where a sequence-based serotype adds information. A WHO status describes the allele's official assignment, not the reliability of the HATS serotype.

A second badge, IPD serotype, answers a different question: whether IPD-IMGT/HLA itself lists the serotype assignment for the allele (IPD carries a copy of the HATS output). IPD lists it only for alleles with a Full or Serotype qualifier, so an Incomplete, Unassigned or in silico allele has none there even when WHO's own antigen agrees with the serotype; and IPD withholds it for Full or Serotype alleles whose WHO antigen conflicts with it. The IPD-IMGT/HLA Comparison tab under View Data lists every case of both kinds.

Bw4 and Bw6 are separate public epitopes

Bw4 and Bw6 are public epitopes shared across most HLA-B antigens (and a few HLA-A). They form their own codominant system and sit outside the broad / split / serotype hierarchy, so an allele can carry a Bw4 or Bw6 assignment in addition to its serological assignment.

Serotypes and eplet matching

Serotypes complement epitope-based (eplet) matching, which estimates compatibility from the load of mismatched eplets between donor and recipient. A serotype collapses an allele's epitope variation into a single, named serological specificity defined by the same membrane-distal, antibody-accessible residues (DEP), giving most alleles a standardized antigen a lab can use without specialized software, allele-level typing, or eplet expertise, and remaining complementary to eplet matching where it is performed.

An evolving classification

Serotype definition is an ongoing effort. The 2024 update validated 20 new antigens against patient antibody data, and the 2025 study added epitope positions 103 and 109, allowing nearly all common HLA-B antigens to be defined at the most precise (Full) level, and proposed 18 further antigens across HLA-B and HLA-DP. Newly accepted specificities are folded into WHO nomenclature (most recently the 2026 report) and the IPD-IMGT/HLA database, so the set of serotypes continues to grow with each release.

Example: the A9 family

Broad

A9

Split

A23

Split

A24

Serotype

A2301

Serotype

A2304

Serotype

A2402

Serotype

A2403

Serotype

A2404

Serotype

A2405

Serotype

A2408

Serotype

A2410

Serotype

A2414

Serotype

A2423

Serotype

A2424