What "two-field" HLA typing means, and why people still say 4-digit
A two-field HLA result is a name with two colon-separated numbers after the gene, such as A*02:01: the allele group, then the specific protein. "4-digit" is the older word for the same idea, from the years when each field was exactly two digits and names were written without colons, so A*02:01 was A*0201.
The two terms describe the same level of the nomenclature, but only "two-field" is still accurate. Since April 2010 a field can have two, three or four digits, so counting digits no longer tells you how precise a name is.
Where "4-digit" came from
The four-digit convention for alleles encoding different proteins was introduced in the 1987 Nomenclature Report. For more than twenty years an allele was written as a run of digits: the first two for the allele group, the next two for the protein, and further pairs for finer differences. A*0201 was "4-digit typing", A*020101 "6-digit", and so on.
The WHO Nomenclature Committee for Factors of the HLA System decided in 2008 to put colons between the fields, and the change took effect in April 2010. The April 2010 update page gives the conversions: A*3301 became A*33:01, A*260101 became A*26:01:01, and so on. Leading zeros already in a name were kept; no new ones were added.
Once fields were delimited, they no longer had to be two digits long, and they are not. The guide on converting pre-2010 names covers the mechanics.
What the two fields fix
The allele naming rules at hla.alleles.org define the fields:
| Field | Example in A*02:01 | What it separates |
|---|---|---|
| First | 02 | The allele group, which often corresponds to the serological antigen |
| Second | 01 | Subtypes, numbered in the order their sequences were determined |
Two alleles whose names differ in either of the first two fields must differ by at least one nucleotide substitution that changes the amino acid sequence of the protein. So a two-field name identifies a protein sequence. The third and fourth fields separate synonymous coding changes and non-coding changes, which do not alter the protein.
That is why two-field names are the working unit for so much downstream use. Match grades at allele level compare two-field names, and the CPIC pharmacogenomic guideline records key on two-field names such as B*57:01.
Two-field is a protein, not a single allele
A two-field name is usually a set of named alleles that share a protein. In IPD-IMGT/HLA release 3.66.0, A*02:01 covers 519 full-length alleles, B*07:02 covers 255 and DRB1*15:01 covers 89. A few are small: A*01:02 covers 4.
Some alleles have no further fields at all. Names are only as long as they need to be, so an allele with no synonymous or non-coding relatives keeps a two-field name. A*03:06 is an assigned allele in release 3.66.0 with no third field. The typing resolution guide separates "how long the name is" from "how much of the gene was examined".
Where the digit count breaks
Counting digits gives the wrong answer for a large share of current names.
The second field passed 99 long ago. The 2010 update says that families reaching 100 alleles continue sequentially, so A*24:99 is followed by A*24:100. In release 3.66.0 more than 4,500 names at each of HLA-A, -B and -C have a second field of three or more digits, and 330 HLA-A names and 301 HLA-C names have a four-digit second field. C*07:1245:01:01 is one of them. A*24:100 is a two-field name with five digits.
The first field can be three or four digits. HLA-DPB1 alleles from the old system were renamed into new families in 2010: DPB1*0102 became DPB1*100:01. In release 3.66.0, 2,065 DPB1 names have a first field of three or more digits. DPB1*104:01 covers 27 alleles, and DPB1*1537:01:01 is an assigned allele.
Some rollover names moved into existing families. The 2002 rollover family A*92 was folded back in 2010: A*9201 became A*02:101. Read as digits, A*9201 looked like a four-digit A*92 allele; it is now a two-field name with five digits under A*02.
So "4-digit" and "two-field" agree only for names whose fields happen to be two digits each. A rule written as "keep the first four digits" or "truncate to six characters" will corrupt names like these.
When the old term still appears
You will still meet "4-digit" and "high-resolution 4-digit" in older papers, protocols and kit documentation, and in search queries. Treat it as a synonym for two-field when it describes a level, and check the actual names when it describes a format. A dataset that says "4-digit" may store A*0201-style names, which need conversion before comparison, or colon-delimited two-field names under an old label.
Inside software, avoid digit counts entirely. Split on the colon, count fields, and keep any expression suffix. A*24:09N is a two-field name whose suffix matters; stripping it to make a "4-digit" value turns a null allele into an apparently expressed one.
Reducing a longer name to two fields
When you need the two-field form of a longer name:
- Split the name at the
*into gene and fields. - Keep the first two colon-separated fields, whatever their length.
- Keep an expression suffix only when every allele under the two-field name shares it.
A*24:09NstaysA*24:09N. - Do not reduce G or P group names, multiple allele codes or
XXcodes by string surgery. They are sets, not alleles, and need to be resolved against the release.
GET /v1/allele/{name} returns the two-field form, the member count and the resolution level for any name in the pinned release, and the API reference lists the batch calls.
Frequently asked questions
Is two-field the same as 4-digit HLA typing?
They describe the same level, the allele group plus the protein. "Two-field" is the current term because since April 2010 each field can have more than two digits.
Does two-field mean high resolution?
A two-field name fixes the protein sequence. Formal resolution terms such as "high resolution" have their own published definitions, so check those and your protocol rather than inferring resolution from field count.
Why does A*24:100 have five digits but only two fields?
The second field passed 99, and the 2010 rules continue numbering sequentially. It is a two-field name; the digit count is irrelevant.
Can I convert a name to two fields by keeping four digits?
No. Many current names have three- or four-digit fields, such as DPB1*104:01 and C*07:1245:01:01. Split on the colons and keep the first two fields.
Sources
- https://hla.alleles.org/pages/nomenclature/naming_alleles/
- https://hla.alleles.org/pages/nomenclature/nomenclature_update_april_2010/
- https://github.com/ANHIG/IMGTHLA/blob/Latest/README.md
- https://github.com/ANHIG/IMGTHLA/tree/Latest/allelelist
HLA-Verify is a research-and-evaluation tool for nomenclature and reference-release validation. It is not a medical device and this guide is not clinical advice. Send allele names, never patient identifiers.