HLA-DRB1 - the polymorphic beta chain, one of several that can make an HLA-DR dimer, and the reason a chain cannot be inferred from a flow result
also called HLA-DRB1 · HLA class II histocompatibility antigen DRB1 beta chain · P01911
HLA-DRB1 is the highly variable half of the HLA-DR marker - it differs more between people than almost any other human gene. It also is not the only beta chain that can do the job, which is why you cannot look at an HLA-DR flow result and say which gene made it.
The same thing, for a scientist
HLA-DRB1 (UniProt **P01911**, DRB1_HUMAN, **266 aa**, single reviewed human record, primary gene name HLA-DRB1, no listed synonyms) encodes the most commonly expressed beta chain of the HLA-DR heterodimer [E1]. The locus is among the most polymorphic in the human genome, and **HLA-DRB3, DRB4 and DRB5 also produce beta chains that pair with HLA-DRA to form surface HLA-DR**. **That one-to-many relationship is the identifier lesson of this entry.** For CD15 the failure is that *no* gene encodes the antigen. For HLA-DR it is that **several** do, and an anti-HLA-DR antibody typically recognises a monomorphic determinant on the assembled dimer, so the assay cannot report which beta locus contributed. A pipeline that maps HLA-DR to HLA-DRB1 is not making a small approximation; it is discarding the DRB3/4/5 contribution and the allele entirely. **No source read on this beat names HLA-DRB1 in a KMT2A context.** The only chain any source names is HLA-DRA [see `gene-hla-dra`]. A bounded search returns 2 records for `(HLA-DRA OR HLA-DRB1) AND (KMT2A OR MLL) AND leukemia` and the HLA-DRB1-relevant one is an alternative-donor transplantation study, i.e. HLA matching, not blast phenotype [E2].
What a canonical record does and does not represent
UniProt gives one reviewed record for HLA-DRB1 while the locus has thousands of named alleles. So data.length_aa: 266 is a statement about which reference record this entry used, not about a patient's protein. This matters for the project's verify-accessions.py length check: it will pass, and passing means the record was read correctly, not that the number describes anyone's biology.
The honest formulation for any HLA measurement in this graph:
- flow 'HLA-DR' ->
chain: unstated, and do not resolve it - a stated chain -> record it
- an allele (e.g. DRB1*15:01) -> record the allele, and note that it is a genotype, not a surface-expression measurement
| uniprot | P01911 |
|---|---|
| length AA | 266 |
| gene primary | HLA-DRB1 |
| polymorphism | among the most polymorphic loci in the human genome; one canonical UniProt record stands for thousands of alleles |
| partner chain | HLA-DRA (P01903) |
| resolution note | gene_exact:HLA-DRB1 AND organism_id:9606 AND reviewed:true returned exactly one row on 2026-09-20 whose primary gene name equals HLA-DRB1 and whose length is 266. The record is a reference allele; the length check verifies the lookup, not the biology. |
| kmt2a literature | none reporting blast expression as of 2026-09-20 (bounded counted absence, controls passed) |
| gene symbol | HLA-DRB1 |
| gene symbol note | promoted from gene_primary 2026-09-20: verify-accessions.py reads data.gene_symbol, so a gene_primary-only entry was being length-checked or id-inferred rather than symbol-asserted |
uniprot gene synonyms
[]
other beta chains forming DR
[ "HLA-DRB3", "HLA-DRB4", "HLA-DRB5" ]
depmap kmt2a selectivity
{
"chronos_mean_kmt2a_rearranged": 0.0346,
"chronos_mean_other_leukaemia": 0.0815,
"difference": -0.0469,
"pan_essentiality_all_lines": 0.0554,
"selectivity_rank": 3726,
"rank_denominator": 17728,
"provenance": "Joined 2026-09-21 from analyses/depmap-kmt2a-selective-scan-full (generated 2026-09-19T10:12:06Z), the project's own genome-wide scan over 11 KMT2A-rearranged and 43 other leukaemia DepMap lines. NOT re-fetched and NOT independent of that scan: every caveat it carries applies here, including that the KMT2A-rearranged arm is a small number of lines drawn from nine individuals, that the rank denominator is 17,728 genes, and that a difference is not a dependency. Added because only 26 of 308 gene entries carried this number, which made any KMT2A-selectivity question answerable for 8% of the corpus.",
"how_to_read": "A negative difference means MORE required in KMT2A-rearranged lines than in other leukaemia lines. A rank near 17,728 is ANTI-selective. Neither is evidence of a fusion-driven dependency on its own: check pan_essentiality_all_lines before calling anything selective, and note that a paralogue-redundant gene can score near zero for reasons that have nothing to do with this disease - see ana-the-paralogue-redundancy-excuse-is-not-tested-and-my-proxy-decided-the-answer."
}- **Never infer HLA-DRB1 from a flow HLA-DR result.** Several DRB loci form the dimer and the antibody reads a monomorphic determinant.
- **An allele is a genotype, not an expression level.** HLA typing data in a clinical record says nothing about how much class II a blast displays.
- Do any KMT2A-rearranged cases show class II loss, which would be an immune-evasion phenotype relevant to every T-cell-engaging therapy in this graph? Not measured anywhere found on this beat.
- Is the beta chain contributing to surface HLA-DR on blasts ever determined in practice? If assays cannot distinguish it, the graph should stop recording HLA-DR as if a gene were implied.
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
The reviewed human UniProt record for HLA-DRB1 is P01911 (DRB1_HUMAN), primary gene name HLA-DRB1, no listed gene synonyms, 266 aa, protein name 'HLA class II histocompatibility antigen, DRB1 beta chain (Human leukocyte antigen DRB1)'.
UniProtKB reviewed entry P01911 (DRB1_HUMAN) · UniProt Consortium · UniProtKB 2026What this evidence cannot show
Fetched live from the UniProt REST API on 2026-09-20 with fields accession, gene_primary, gene_synonym, protein_name, length; exactly one reviewed human row whose primary gene name equals HLA-DRB1. **The single canonical record stands for a locus with thousands of alleles**, so the 266 aa figure identifies the reference sequence used and not the protein in any individual. HLA-DRB3/4/5 have their own records and also form DR dimers.
Evidence that argues against this (1)
- Because several DRB loci produce surface HLA-DR, asserting HLA-DRB1 as 'the' beta chain is an approximation in the one-to-many direction, exactly mirroring the many-to-one problem that makes CD15 unresolvable. Both directions of the gene-to-marker mapping fail on this beat. UniProt Consortium 2026
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset
As of 2026-09-20, PubMed returns 2 records for `(HLA-DRA OR HLA-DRB1) AND (KMT2A OR MLL) AND leukemia` - a transplantation alternative-donor study (PMID 25402415) and a chromatin study of MLL/COMPASS at CIITA and MHC-II promoters (PMID 20181089) - against 44 for `"HLA-DR" AND (KMT2A OR MLL)`; no study found reports HLA-DRB1 expression on KMT2A-rearranged blasts.
Q48 surface-antigen beat: bounded counted-absence sweep, PubMed E-utilities and Europe PMC REST · Q48-surface-antigens · Oncofusion knowledge graph (internal measurement, 2026-09-20) 2026What this evidence cannot show
**Bounded counted absence.** Date 2026-09-20; tool NCBI PubMed E-utilities esearch db=pubmed; `querytranslation` read back. **Rule 67 controls passed through the identical code path:** `HLA-DRA OR HLA-DRB1` alone = 12,630, `KMT2A OR MLL` alone = 9,229. Both records were title-checked. **Residual:** the 44 `"HLA-DR"` records were title-checked and not read, and a paper could report a DRB1 result without naming the gene in its title.
Evidence that argues against this (1)
- HLA-DRB1 has an enormous literature (part of the 12,630) that is overwhelmingly about transplantation matching and autoimmune disease association. Its near-absence from the leukaemia-phenotype literature reflects a field boundary rather than an unexplored question about blasts. Q48-surface-antigens 2026
class II transactivator acting at the MHC-II promoter SXY module
most common beta chain; DRB3/4/5 also form DR dimers
the two chains pair to form the surface HLA-DR heterodimer; DRB3/4/5 can substitute for DRB1
- supports →A CD number names a reagent cluster, not a molecule - and four different things can sit behind one
the one-to-many direction: several DRB loci make the same surface marker, so a marker cannot name a gene either