HLA in the 1960s: Just Getting Started
In the 1960’s, researchers started really working to evaluate the antigens on white blood cells.
The first International Workshop on Histocompatibility (IWH) was held in 1964 at Duke University but no clear result patterns were observed, though assay techniques were shared.1
The sharing of assay techniques was extremely valuable given that there were no real reference reagents or standardized procedures up until this point.3 The shared testing techniques included leukoagglutination, complement fixation, and the newly developed microcytotoxicity test from Paul Terasaki. These assays are considered serology testing, which use antibodies to identify cell surface antigens.
Once laboratories had a set of shared tests, the second IWH (1965) focused on results gleaned from those tests. Several potential ‘systems’ were named, but the complexity of the antigens on white blood cells still wasn’t clear. Walter Bodmer and Rose Payne described a system called LA (LA1, LA2, LA3, etc) while Jon van Rood described a system called FOUR (4a4b).1
The third IWH (1967) used a family study to answer the question of systems. They discovered that the LA and FOUR systems were both part of the same system (the HLA/MHC system, ultimately).1 It was following the third IWH that the HLA Nomenclature Committee met for the first time (aided by the World Health Organization).
If you haven’t heard the word ‘nomenclature’ before, it basically means “naming convention”. HLA nomenclature is the system for naming HLA specificities (antigens), alleles, and genes as they are discovered. Each piece of the name tells us something about the antigen and it’s corresponding genetics.
You can look at this field and the story of HLA nomenclature as one of endless problem solving. For every problem researchers and the Nomenclature Committee encountered in their pursuit to understand why things were happening, they responded with new nomenclature rules that incorporated their discovery.
The nomenclature report summary table at the end of each decade identifies the problems and corresponding solutions encountered with each nomenclature meeting.
As testing techniques advance, you’ll see the HLA system increase in complexity. In the 1960s, serology testing was the main test type in use.
Why Start a Nomenclature Committee?
The nomenclature committee created a unified understanding of the HLA system we know and love today.
The first report from the Nomenclature Committee did a few key things:
- It unified terminology within the field
- It clarified how we should notate HL-A antigens, phenotypes, and genotypes
- It described what was needed to verify the identity of new antigen specificities and introduced a pathway for getting new antigen specificities named.
This first report offered a new name for the system of interest: HL-A, meaning Histocompatibility Locus – A.
This first report also told us that antigen specificities would be given a numerical value in sequence, beginning with 1 (aka HL-A1, HL-A2, etc).
Specificities that were already well known in the field were fit into this naming convention and given official names, which condensed the variety of names a single specificity previously had (thank goodness).
Any future antigen specificities must be submitted to the Nomenclature Committee for approval by meeting certain analysis and sample requirements.
Why Implement a Standard Naming Convention
The name you use to reference a given antigen should be the same everywhere. This greatly reduces confusion during collaboration.
Think of how many nicknames your friends probably have. I’m not going to know all of the nicknames but we need to know we’re talking about the same person.
So how do we do that?
How do you keep track of what you’re talking about if you all have different names for it? Answer: you standardize the naming.
We use standardized nomenclature in HLA to make sure we’re talking about the same thing. We’ll know we’re testing on and talking about the same A2 if we agree that it’s name is A2.
Up until this point each laboratory had been individually naming antigens as they identified it for themselves, which made communicating about any given antigen more difficult. HL-A2, previously known as MAC or LA2, was the first antigen discovered in the HLA system and had several different names before being dubbed HL-A2 by the Nomenclature Committee.
What is Serology Testing? What Does This Mean for HLA Typing?
Serology testing is a style of test that measures elements in the blood (antibodies, antigens, proteins, etc).
HLA serology typing uses known antibodies to identify the unknown HLA specificities on a patient’s cells. This requires isolating the patient’s cells (generally from blood samples) in order to perform this testing.
In the 1960s, serology typing was the main style of testing. Additional HLA testing styles developed during the following decades that would change the way we understood HLA, meaning the nomenclature changed as well.
Nomenclature Report Summaries from the 1960’s
Standardized nomenclature gave us all a starting point for communication and, as we progressed through decades of research (and each additional IWH meeting), it allowed data from each laboratory to be incorporated into a single understanding of what the HLA system was.
By the end of the 60’s many labs knew they were working on the same system (and had a name for that system, though they still didn’t have an inkling at how vast it truly was). They also had a set of serology tests that yielded similar results across laboratories, and they could refer to a known set of specificities now that they had a naming convention:
This was our jumping off point into the 1970’s.
References
- Terasaki PI, Dausset J. Payne R, van Rood JJ, van Leeuwen A, Amos DB, Walford RL, Kissmeyer-Nielsen F, Svejgaard A, Batchelor JR, Bach FH. 1990. History of HLA: Ten Recollections.. Los Angeles (CA): The Regents of the University of California.
- WHO Nomenclature Committee (1968). Nomenclature for factors of the HL-A system, 1968. Bulletin of the World Health Organisation, 39, pp. 483-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2554419/pdf/bullwho00230-0140.pdf
- Rodey, G.E. (2000). HLA Beyond Tears: Introduction to Human Histocompatibility (2nd Ed.). De Novo, Inc. ISBN: 0-9678268-0-2
- You can find a link to all relevant nomenclature reports at https://hla.alleles.org/nomenclature/nomenc_reports.html
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