Shorter CDR3 length explained?


#1

Hello.
Maybe someone has an idea. I have performed TCR repertoire on blood from several patients with an autoimmune, genetic, disorder.
I have found they have a shorter CDR3B length than healthy controls (43.7 vs. 43.4 nucleotides. p<0.01)
BUT there are no differences in number of N insertions or deletions.
What else can explain a shorter TCR?


#2

One way would just be to use TRBD1 a bit more often, as it’s shorter than TRBD2:

>K02545|TRBD1*01|Homo sapiens|F|D-REGION|82..93|12 nt|1| | | | |12+0=12| | | 
gggacagggggc 
>X02987|TRBD2*01|Homo sapiens|F|D-REGION|140..155|16 nt|1| | | | |16+0=16| | | 
gggactagcggggggg

However when you say that insertions/deletions are the same, you have to appreciate that those values are an artifact of how the sequences look in the final rearrangement, not actually what happened - e.g. you can’t tell the difference between a base being removed and then the same base being reintroduced.

If you combine that fact with two very small, very similar TRBD genes (which you won’t be able to distinguish in the majority of cases), it’s entirely possible that there are actually significant differences in non-templated insertion/deletions, and you’re just not able to see it.