Question: If my clonotype has multiple alpha and beta chains (for example 1 alpha chain and 2 beta chains), what do I do? Should I discard the clonotype? Or maybe just pick one of the chains?
Answer: Biologically, some fraction of T cells are known to express 2 alpha + 1 beta or 1 alpha + 2 beta chains (Ref1, Ref2). Similarly, there is evidence that some B cells express more than 1 heavy or light chains (Ref3).
Therefore, if you find a large clone that expresses two chains of the same type, it is unlikely that it is caused by technical artifacts such as multiplets, PCR chimeras, etc and it might be a biological event. On the other hand, cases where we see a more complex mixture of chain types such as 4 or more productive contigs are biologically unlikely and may be attributed to technical artifacts.
In older Cell Ranger versions (3.0 or lower) outputs, you may find these clonotypes output by Cell Ranger and can choose to ignore these clonotypes from downstream processing. Cell Ranger version 3.1 or higher assigns low confidence to all contigs in cells that express 4 or more productive chains as these are less biologically likely. The cells with 4 or more productive contigs are therefore not included in the output clonotypes.